Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2022

01-12-2022 | Lymphoma | Review

Altered pathways and targeted therapy in double hit lymphoma

Authors: Yuxin Zhuang, Jinxin Che, Meijuan Wu, Yu Guo, Yongjin Xu, Xiaowu Dong, Haiyan Yang

Published in: Journal of Hematology & Oncology | Issue 1/2022

Login to get access

Abstract

High-grade B-cell lymphoma with translocations involving MYC and BCL2 or BCL6, usually referred to as double hit lymphoma (DHL), is an aggressive hematological malignance with distinct genetic features and poor clinical prognosis. Current standard chemoimmunotherapy fails to confer satisfying outcomes and few targeted therapeutics are available for the treatment against DHL. Recently, the delineating of the genetic landscape in tumors has provided insight into both biology and targeted therapies. Therefore, it is essential to understand the altered signaling pathways of DHL to develop treatment strategies with better clinical benefits. Herein, we summarized the genetic alterations in the two DHL subtypes (DHL-BCL2 and DHL-BCL6). We further elucidate their implications on cellular processes, including anti-apoptosis, epigenetic regulations, B-cell receptor signaling, and immune escape. Ongoing and potential therapeutic strategies and targeted drugs steered by these alterations were reviewed accordingly. Based on these findings, we also discuss the therapeutic vulnerabilities that coincide with these genetic changes. We believe that the understanding of the DHL studies will provide insight into this disease and capacitate the finding of more effective treatment strategies.
Literature
1.
2.
Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, Scott DW, Tan KL, Steidl C, Sehn LH, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(28):3452–9.
3.
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90.PubMedPubMedCentral
4.
Swerdlow SH. Diagnosis of “double hit” diffuse large B-cell lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma: when and how, FISH versus IHC. Hematol Am Soc Hematol Educ Program. 2014;2014(1):90–9.
5.
Sesques P, Johnson NA. Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Blood. 2017;129(3):280–8.PubMed
6.
Ma Z, Niu J, Cao Y, Pang X, Cui W, Zhang W, Li X. Clinical significance of ‘double-hit’ and ‘double-expression’ lymphomas. J Clin Pathol. 2020;73(3):126–38.PubMed
7.
Merron B, Davies A. Double hit lymphoma: How do we define it and how do we treat it? Best Pract Res Clin Haematol. 2018;31(3):233–40.PubMed
8.
Copie-Bergman C, Cuilliere-Dartigues P, Baia M, Briere J, Delarue R, Canioni D, Salles G, Parrens M, Belhadj K, Fabiani B, et al. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study. Blood. 2015;126(22):2466–74.PubMed
9.
McPhail ED, Maurer MJ, Macon WR, Feldman AL, Kurtin PJ, Ketterling RP, Vaidya R, Cerhan JR, Ansell SM, Porrata LF, et al. Inferior survival in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements is not associated with MYC/IG gene rearrangements. Haematologica. 2018;103(11):1899–907.PubMedPubMedCentral
10.
Pedersen MO, Gang AO, Poulsen TS, Knudsen H, Lauritzen AF, Nielsen SL, Klausen TW, Norgaard P. MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations. Eur J Haematol. 2014;92(1):42–8.PubMed
11.
Aukema SM, Kreuz M, Kohler CW, Rosolowski M, Hasenclever D, Hummel M, Kuppers R, Lenze D, Ott G, Pott C, et al. Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma. Haematologica. 2014;99(4):726–35.PubMedPubMedCentral
12.
Rosenwald A, Bens S, Advani R, Barrans S, Copie-Bergman C, Elsensohn MH, Natkunam Y, Calaminici M, Sander B, Baia M, et al. Prognostic significance of MYC rearrangement and translocation partner in diffuse large B-cell lymphoma: a study by the lunenburg lymphoma biomarker consortium. J Clin Oncol Off J Am Soc Clin Oncol. 2019;37(35):3359–68.
13.
Herrera AF, Mei M, Low L, Kim HT, Griffin GK, Song JY, Merryman RW, Bedell V, Pak C, Sun H, et al. Relapsed or Refractory double-expressor and double-hit lymphomas have inferior progression-free survival after autologous stem-cell transplantation. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35(1):24–31.
14.
Hu S, Xu-Monette ZY, Tzankov A, Green T, Wu L, Balasubramanyam A, Liu WM, Visco C, Li Y, Miranda RN, et al. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from the International DLBCL Rituximab-CHOP Consortium Program. Blood. 2013;121(20):4021–31 (quiz 4250).PubMedPubMedCentral
15.
Sha C, Barrans S, Cucco F, Bentley MA, Care MA, Cummin T, Kennedy H, Thompson JS, Uddin R, Worrillow L, et al. Molecular high-grade B-cell lymphoma: defining a poor-risk group that requires different approaches to therapy. J Clin Oncol Off J Am Soc Clin Oncol. 2019;37(3):202–12.
16.
Scott DW, King RL, Staiger AM, Ben-Neriah S, Jiang A, Horn H, Mottok A, Farinha P, Slack GW, Ennishi D, et al. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology. Blood. 2018;131(18):2060–4.PubMedPubMedCentral
17.
Huang W, Medeiros LJ, Lin P, Wang W, Tang G, Khoury J, Konoplev S, Yin CC, Xu J, Oki Y, et al. MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas. Mod Pathol Off J US Can Acad Pathol. 2018;31(9):1470–8.
18.
Pillai RK, Sathanoori M, Van Oss SB, Swerdlow SH. Double-hit B-cell lymphomas with BCL6 and MYC translocations are aggressive, frequently extranodal lymphomas distinct from BCL2 double-hit B-cell lymphomas. Am J Surg Pathol. 2013;37(3):323–32.PubMed
19.
Lacy SE, Barrans SL, Beer PA, Painter D, Smith AG, Roman E, Cooke SL, Ruiz C, Glover P, Van Hoppe SJL, et al. Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report. Blood. 2020;135(20):1759–71.PubMedPubMedCentral
20.
Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, Lawrence MS, Roemer MGM, Li AJ, Ziepert M, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018;24(5):679–90.PubMedPubMedCentral
21.
Schmitz R, Wright GW, Huang DW, Johnson CA, Phelan JD, Wang JQ, Roulland S, Kasbekar M, Young RM, Shaffer AL, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018;378(15):1396–407.PubMedPubMedCentral
22.
Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, Wang JQ, Schmitz R, Morin RD, Tang J, et al. A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications. Cancer cell. 2020;37(4):551–68.PubMedPubMedCentral
23.
Cucco F, Barrans S, Sha C, Clipson A, Crouch S, Dobson R, Chen Z, Thompson JS, Care MA, Cummin T, et al. Distinct genetic changes reveal evolutionary history and heterogeneous molecular grade of DLBCL with MYC/BCL2 double-hit. Leukemia. 2020;34(5):1329–41.PubMed
24.
Li S, Desai P, Lin P, Yin CC, Tang G, Wang XJ, Konoplev SN, Khoury JD, Bueso-Ramos CE, Medeiros LJ. MYC/BCL6 double-hit lymphoma (DHL): a tumour associated with an aggressive clinical course and poor prognosis. Histopathology. 2016;68(7):1090–8.PubMed
25.
Ye Q, Xu-Monette ZY, Tzankov A, Deng L, Wang X, Manyam GC, Visco C, Montes-Moreno S, Zhang L, Dybkær K, et al. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma. Oncotarget. 2016;7(3):2401–16.PubMed
26.
Ennishi D, Jiang A, Boyle M, Collinge B, Grande BM, Ben-Neriah S, Rushton C, Tang J, Thomas N, Slack GW, et al. Double-hit gene expression signature defines a distinct subgroup of germinal center B-cell-like diffuse large B-cell lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2019;37(3):190–201.
27.
Frosch ZAK, Landsburg DJ. Molecular risk stratification in aggressive B-cell lymphomas. J Clin Oncol Off J Am Soc Clin Oncol. 2020;38(18):2014–7.
28.
Frosch ZAK, Dwivedy Nasta S, Schuster SJ, Svoboda J, Barta SK, Gerson JN, Chong EA, Ayers EC, Rhodes JM, Koike A, et al. Outcomes for double hit lymphoma patients identified via routine vs selective testing for MYC rearrangement. Blood. 2019;134(Supp 1):1607–1607.
29.
30.
Green TM, Young KH, Visco C, Xu-Monette ZY, Orazi A, Go RS, Nielsen O, Gadeberg OV, Mourits-Andersen T, Frederiksen M, et al. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(28):3460–7.
31.
Torka P, Kothari SK, Sundaram S, Li S, Medeiros LJ, Ayers EC, Landsburg DJ, Bond DA, Maddocks KJ, Giri A, et al. Outcomes of patients with limited-stage aggressive large B-cell lymphoma with high-risk cytogenetics. Blood Adv. 2020;4(2):253–62.PubMedPubMedCentral
32.
Petrich AM, Gandhi M, Jovanovic B, Castillo JJ, Rajguru S, Yang DT, Shah KA, Whyman JD, Lansigan F, Hernandez-Ilizaliturri FJ, et al. Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis. Blood. 2014;124(15):2354–61.PubMed
33.
Oki Y, Noorani M, Lin P, Davis RE, Neelapu SS, Ma L, Ahmed M, Rodriguez MA, Hagemeister FB, Fowler N, et al. Double hit lymphoma: the MD Anderson cancer center clinical experience. Br J Haematol. 2014;166(6):891–901.PubMed
34.
Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, et al. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015;170(4):504–14.PubMed
35.
D’Angelo CR, Hanel W, Chen Y, Yu M, Yang D, Guo L, Karmali R, Burkart M, Ciccosanti C, David K, et al. Impact of initial chemotherapy regimen on outcomes for patients with double-expressor lymphoma: a multi-center analysis. Hematol Oncol. 2021;39(4):473–82.PubMed
36.
Landsburg DJ, Falkiewicz MK, Maly J, Blum KA, Howlett C, Feldman T, Mato AR, Hill BT, Li S, Medeiros LJ, et al. Outcomes of patients with double-hit lymphoma who achieve first complete remission. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35(20):2260–7.
37.
Sun H, Savage KJ, Karsan A, Slack GW, Gascoyne RD, Toze CL, Sehn LH, Abou Mourad Y, Barnett MJ, Broady RC, et al. Outcome of patients with non-hodgkin lymphomas with concurrent MYC and BCL2 rearrangements treated with CODOX-M/IVAC with rituximab followed by hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk. 2015;15(6):341–8.PubMed
38.
Li S, Lin P, Fayad LE, Lennon PA, Miranda RN, Yin CC, Lin E, Medeiros LJ. B-cell lymphomas with MYC/8q24 rearrangements and IGH@BCL2/t(14;18)(q32;q21): an aggressive disease with heterogeneous histology, germinal center B-cell immunophenotype and poor outcome. Mod Pathol Off J US Can Acad Pathol. 2012;25(1):145–56.
39.
Laude MC, Lebras L, Sesques P, Ghesquieres H, Favre S, Bouabdallah K, Croizier C, Guieze R, Drieu La Rochelle L, Gyan E, et al. First-line treatment of double-hit and triple-hit lymphomas: Survival and tolerance data from a retrospective multicenter French study. Am J Hematol. 2021;96(3):302–11.PubMed
40.
Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, et al. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016;174(5):686–91.PubMedPubMedCentral
41.
Huang W, Medeiros LJ, Lin P, Wang W, Tang G, Khoury J, Konoplev S, Yin CC, Xu J, Oki Y, et al. MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas. Mod Pathol. 2018;31(9):1470–8.PubMed
42.
Zhang J, Vlasevska S, Wells VA, Nataraj S, Holmes AB, Duval R, Meyer SN, Mo T, Basso K, Brindle PK, et al. The CREBBP acetyltransferase is a haploinsufficient tumor suppressor in B-cell lymphoma. Cancer Discov. 2017;7(3):322–37.PubMedPubMedCentral
43.
Zhang J, Dominguez-Sola D, Hussein S, Lee JE, Holmes AB, Bansal M, Vlasevska S, Mo T, Tang H, Basso K, et al. Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis. Nat Med. 2015;21(10):1190–8.PubMedPubMedCentral
44.
Brescia P, Schneider C, Holmes AB, Shen Q, Hussein S, Pasqualucci L, Basso K, Dalla-Favera R. MEF2B instructs germinal center development and acts as an oncogene in B cell lymphomagenesis. Cancer Cell. 2018;34(3):453-465.e459.PubMedPubMedCentral
45.
Béguelin W, Popovic R, Teater M, Jiang Y, Bunting KL, Rosen M, Shen H, Yang SN, Wang L, Ezponda T, et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell. 2013;23(5):677–92.PubMedPubMedCentral
46.
Lee CH, Melchers M, Wang H, Torrey TA, Slota R, Qi CF, Kim JY, Lugar P, Kong HJ, Farrington L, et al. Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein. J Exp Med. 2006;203(1):63–72.PubMedPubMedCentral
47.
Zhou JX, Lee CH, Qi CF, Wang H, Naghashfar Z, Abbasi S, Morse HC 3rd. IFN regulatory factor 8 regulates MDM2 in germinal center B cells. J Immunol. 2009;183(5):3188–94.PubMed
48.
Brescia P, Schneider C, Holmes AB, Shen Q, Hussein S, Pasqualucci L, Basso K, Dalla-Favera R. MEF2B instructs germinal center development and acts as an oncogene in B cell lymphomagenesis. Cancer cell. 2018;34(3):453–65.PubMedPubMedCentral
49.
Martinez A, Pittaluga S, Rudelius M, Davies-Hill T, Sebasigari D, Fountaine TJ, Hewitt S, Jaffe ES, Raffeld M. Expression of the interferon regulatory factor 8/ICSBP-1 in human reactive lymphoid tissues and B-cell lymphomas: a novel germinal center marker. Am J Surg Pathol. 2008;32(8):1190–200.PubMedPubMedCentral
50.
Ying CY, Dominguez-Sola D, Fabi M, Lorenz IC, Hussein S, Bansal M, Califano A, Pasqualucci L, Basso K, Dalla-Favera R. MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma. Nat Immunol. 2013;14(10):1084–92.PubMedPubMedCentral
51.
Bouamar H, Abbas S, Lin AP, Wang L, Jiang D, Holder KN, Kinney MC, Hunicke-Smith S, Aguiar RC. A capture-sequencing strategy identifies IRF8, EBF1, and APRIL as novel IGH fusion partners in B-cell lymphoma. Blood. 2013;122(5):726–33.PubMedPubMedCentral
52.
Li H, Kaminski MS, Li Y, Yildiz M, Ouillette P, Jones S, Fox H, Jacobi K, Saiya-Cork K, Bixby D, et al. Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma. Blood. 2014;123(10):1487–98.PubMedPubMedCentral
53.
Zhang J, Grubor V, Love CL, Banerjee A, Richards KL, Mieczkowski PA, Dunphy C, Choi W, Au WY, Srivastava G, et al. Genetic heterogeneity of diffuse large B-cell lymphoma. Proc Natl Acad Sci U S A. 2013;110(4):1398–403.PubMedPubMedCentral
54.
Chen H, Liu H, Qing G. Targeting oncogenic Myc as a strategy for cancer treatment. Signal Transduct Target Ther. 2018;3:5.PubMedPubMedCentral
55.
Sabo A, Kress TR, Pelizzola M, de Pretis S, Gorski MM, Tesi A, Morelli MJ, Bora P, Doni M, Verrecchia A, et al. Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis. Nature. 2014;511(7510):488–92.PubMedPubMedCentral
56.
Xu-Monette ZY, Deng Q, Manyam GC, Tzankov A, Li L, Xia Y, Wang XX, Zou D, Visco C, Dybkaer K, et al. Clinical and biologic significance of MYC genetic mutations in De Novo diffuse large B-cell lymphoma. Clin Cancer Res. 2016;22(14):3593–605.PubMedPubMedCentral
57.
Valera A, Lopez-Guillermo A, Cardesa-Salzmann T, Climent F, Gonzalez-Barca E, Mercadal S, Espinosa I, Novelli S, Briones J, Mate JL, et al. MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Haematologica. 2013;98(10):1554–62.PubMedPubMedCentral
58.
Stasik CJ, Nitta H, Zhang W, Mosher CH, Cook JR, Tubbs RR, Unger JM, Brooks TA, Persky DO, Wilkinson ST, et al. Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma. Haematologica. 2010;95(4):597–603.PubMedPubMedCentral
59.
Amin RH, Schlissel MS. Foxo1 directly regulates the transcription of recombination-activating genes during B cell development. Nat Immunol. 2008;9(6):613–22.PubMedPubMedCentral
60.
Trinh DL, Scott DW, Morin RD, Mendez-Lago M, An J, Jones SJ, Mungall AJ, Zhao Y, Schein J, Steidl C, et al. Analysis of FOXO1 mutations in diffuse large B-cell lymphoma. Blood. 2013;121(18):3666–74.PubMedPubMedCentral
61.
Xie L, Ushmorov A, Leithauser F, Guan H, Steidl C, Farbinger J, Pelzer C, Vogel MJ, Maier HJ, Gascoyne RD, et al. FOXO1 is a tumor suppressor in classical Hodgkin lymphoma. Blood. 2012;119(15):3503–11.PubMed
62.
Sander S, Chu VT, Yasuda T, Franklin A, Graf R, Calado DP, Li S, Imami K, Selbach M, Di Virgilio M, et al. PI3 kinase and FOXO1 transcription factor activity differentially control b cells in the germinal center light and dark zones. Immunity. 2015;43(6):1075–86.PubMed
63.
Szydlowski M, Kiliszek P, Sewastianik T, Jablonska E, Bialopiotrowicz E, Gorniak P, Polak A, Markowicz S, Nowak E, Grygorowicz MA, et al. FOXO1 activation is an effector of SYK and AKT inhibition in tonic BCR signal-dependent diffuse large B-cell lymphomas. Blood. 2016;127(6):739–48.PubMed
64.
Morin RD, Assouline S, Alcaide M, Mohajeri A, Johnston RL, Chong L, Grewal J, Yu S, Fornika D, Bushell K, et al. Genetic Landscapes of relapsed and refractory diffuse large B-cell lymphomas. Clin Cancer Res. 2016;22(9):2290–300.PubMed
65.
Ushmorov A, Wirth T. FOXO in B-cell lymphopoiesis and B cell neoplasia. Semin Cancer Biol. 2018;50:132–41.PubMed
66.
Hodson DJ, Shaffer AL, Xiao W, Wright GW, Schmitz R, Phelan JD, Yang Y, Webster DE, Rui L, Kohlhammer H, et al. Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2. Proc Natl Acad Sci USA. 2016;113(14):E2039-2046.PubMedPubMedCentral
67.
Karnowski A, Chevrier S, Belz GT, Mount A, Emslie D, D’Costa K, Tarlinton DM, Kallies A, Corcoran LM. B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1. J Exp Med. 2012;209(11):2049–64.PubMedPubMedCentral
68.
Corcoran L, Emslie D, Kratina T, Shi W, Hirsch S, Taubenheim N, Chevrier S. Oct2 and Obf1 as facilitators of B: T cell collaboration during a humoral immune response. Front Immunol. 2014;5:108.PubMedPubMedCentral
69.
Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15(1):49–63.PubMed
70.
Schuetz JM, Johnson NA, Morin RD, Scott DW, Tan K, Ben-Nierah S, Boyle M, Slack GW, Marra MA, Connors JM, et al. BCL2 mutations in diffuse large B-cell lymphoma. Leukemia. 2012;26(6):1383–90.PubMed
71.
Ennishi D, Mottok A, Ben-Neriah S, Shulha HP, Farinha P, Chan FC, Meissner B, Boyle M, Hother C, Kridel R, et al. Genetic profiling of MYC and BCL2 in diffuse large B-cell lymphoma determines cell-of-origin-specific clinical impact. Blood. 2017;129(20):2760–70.PubMed
72.
Deng X, Gao F, Flagg T, Anderson J, May WS. Bcl2’s flexible loop domain regulates p53 binding and survival. Mol Cell Biol. 2006;26(12):4421–34.PubMedPubMedCentral
73.
Monaco G, Decrock E, Akl H, Ponsaerts R, Vervliet T, Luyten T, De Maeyer M, Missiaen L, Distelhorst CW, De Smedt H, et al. Selective regulation of IP3-receptor-mediated Ca2+ signaling and apoptosis by the BH4 domain of BCL2 versus Bcl-Xl. Cell Death Differ. 2012;19(2):295–309.PubMed
74.
Ding J, Zhang Z, Roberts GJ, Falcone M, Miao Y, Shao Y, Zhang XC, Andrews DW, Lin J. BCL2 and Bax interact via the BH1-3 groove-BH3 motif interface and a novel interface involving the BH4 motif. J Biol Chem. 2010;285(37):28749–63.PubMedPubMedCentral
75.
Fresquet V, Rieger M, Carolis C, Garcia-Barchino MJ, Martinez-Climent JA. Acquired mutations in BCL2 family proteins conferring resistance to the BH3 mimetic ABT-199 in lymphoma. Blood. 2014;123(26):4111–9.PubMed
76.
Guegan JP, Ginestier C, Charafe-Jauffret E, Ducret T, Quignard JF, Vacher P, Legembre P. CD95/Fas and metastatic disease: What does not kill you makes you stronger. Semin Cancer Biol. 2020;60:121–31.PubMed
77.
Takahashi H, Feuerhake F, Kutok JL, Monti S, Dal Cin P, Neuberg D, Aster JC, Shipp MA. FAS death domain deletions and cellular FADD-like interleukin 1beta converting enzyme inhibitory protein (long) overexpression: alternative mechanisms for deregulating the extrinsic apoptotic pathway in diffuse large B-cell lymphoma subtypes. Clin Cancer Res. 2006;12(11 Pt 1):3265–71.PubMed
78.
Razzaghi R, Agarwal S, Kotlov N, Plotnikova O, Nomie K, Huang DW, Wright GW, Smith GA, Li M, Takata K et al: Compromised counterselection by FAS creates an aggressive subtype of germinal center lymphoma. J Exp Med 2021, 218(3).
79.
Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011;476(7360):298–303.PubMedPubMedCentral
80.
Black JC, Van Rechem C, Whetstine JR. Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell. 2012;48(4):491–507.PubMed
81.
Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012;13(5):343–57.PubMedPubMedCentral
82.
Ortega-Molina A, Boss IW, Canela A, Pan H, Jiang Y, Zhao C, Jiang M, Hu D, Agirre X, Niesvizky I, et al. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development. Nat Med. 2015;21(10):1199–208.PubMedPubMedCentral
83.
Velichutina I, Shaknovich R, Geng H, Johnson NA, Gascoyne RD, Melnick AM, Elemento O. EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis. Blood. 2010;116(24):5247–55.PubMedPubMedCentral
84.
Yap DB, Chu J, Berg T, Schapira M, Cheng SW, Moradian A, Morin RD, Mungall AJ, Meissner B, Boyle M, et al. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood. 2011;117(8):2451–9.PubMedPubMedCentral
85.
Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, Paul JE, Boyle M, Woolcock BW, Kuchenbauer F, et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 2010;42(2):181–5.PubMedPubMedCentral
86.
Sahasrabuddhe AA, Chen X, Chung F, Velusamy T, Lim MS, Elenitoba-Johnson KS. Oncogenic Y641 mutations in EZH2 prevent Jak2/beta-TrCP-mediated degradation. Oncogene. 2015;34(4):445–54.PubMed
87.
Beguelin W, Popovic R, Teater M, Jiang Y, Bunting KL, Rosen M, Shen H, Yang SN, Wang L, Ezponda T, et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell. 2013;23(5):677–92.PubMedPubMedCentral
88.
Deng Y, Chen X, Huang C, Chen G, Chen F, Lu J, Shi X, He C, Zeng Z, Qiu Y, et al. EZH2/BCL2 coexpression predicts worse survival in diffuse large B-cell lymphomas and demonstrates poor efficacy to rituximab in localized lesions. J Cancer. 2019;10(9):2006–17.PubMedPubMedCentral
89.
Ennishi D, Takata K, Beguelin W, Duns G, Mottok A, Farinha P, Bashashati A, Saberi S, Boyle M, Meissner B, et al. Molecular and genetic characterization of mhc deficiency identifies EZH2 as therapeutic target for enhancing immune recognition. Cancer Discov. 2019;9(4):546–63.PubMed
90.
Dersh D, Phelan JD, Gumina ME, Wang B, Arbuckle JH, Holly J, Kishton RJ, Markowitz TE, Seedhom MO, Fridlyand N, et al. Genome-wide screens identify lineage- and tumor-specific genes modulating MHC-I- and MHC-II-restricted immunosurveillance of human lymphomas. Immunity. 2021;54(1):116–31.PubMed
91.
Berg T, Thoene S, Yap D, Wee T, Schoeler N, Rosten P, Lim E, Bilenky M, Mungall AJ, Oellerich T, et al. A transgenic mouse model demonstrating the oncogenic role of mutations in the polycomb-group gene EZH2 in lymphomagenesis. Blood. 2014;123(25):3914–24.PubMed
92.
Shi Y, Ma HL, Zhuang YW, Wang XX, Jiang Y, Xu HE. C10ORF12 modulates PRC2 histone methyltransferase activity and H3K27me3 levels. Acta Pharmacol Sin. 2019;40(11):1457–65.PubMedPubMedCentral
93.
94.
Meyer SN, Scuoppo C, Vlasevska S, Bal E, Holmes AB, Holloman M, Garcia-Ibanez L, Nataraj S, Duval R, Vantrimpont T, et al. Unique and shared epigenetic programs of the CREBBP and EP300 acetyltransferases in germinal center B cells reveal targetable dependencies in lymphoma. Immunity. 2019;51(3):535–47.PubMedPubMedCentral
95.
Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A, Trifonov V, Kasper LH, Lerach S, Tang H, Ma J, et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature. 2011;471(7337):189–95.PubMedPubMedCentral
96.
Jiang Y, Ortega-Molina A, Geng H, Ying HY, Hatzi K, Parsa S, McNally D, Wang L, Doane AS, Agirre X, et al. CREBBP inactivation promotes the development of HDAC3-dependent lymphomas. Cancer Discov. 2017;7(1):38–53.PubMed
97.
Garcia-Ramirez I, Tadros S, Gonzalez-Herrero I, Martin-Lorenzo A, Rodriguez-Hernandez G, Moore D, Ruiz-Roca L, Blanco O, Alonso-Lopez D, Rivas JL, et al. Crebbp loss cooperates with Bcl2 overexpression to promote lymphoma in mice. Blood. 2017;129(19):2645–56.PubMedPubMedCentral
98.
Hashwah H, Schmid CA, Kasser S, Bertram K, Stelling A, Manz MG, Muller A. Inactivation of CREBBP expands the germinal center B cell compartment, down-regulates MHCII expression and promotes DLBCL growth. Proc Natl Acad Sci U S A. 2017;114(36):9701–6.PubMedPubMedCentral
99.
Huang YH, Cai K, Xu PP, Wang L, Huang CX, Fang Y, Cheng S, Sun XJ, Liu F, Huang JY, et al. CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis. Signal Transduct Target Ther. 2021;6(1):10.PubMedPubMedCentral
100.
Cerchietti LC, Hatzi K, Caldas-Lopes E, Yang SN, Figueroa ME, Morin RD, Hirst M, Mendez L, Shaknovich R, Cole PA, et al. BCL6 repression of EP300 in human diffuse large B cell lymphoma cells provides a basis for rational combinatorial therapy. J Clin Invest. 2010;120(12):4569–82.PubMedPubMedCentral
101.
Scialdone A, Khazaei S, Hasni MS, Lennartsson A, Gullberg U, Drott K. Depletion of the transcriptional coactivators CREB-binding protein or EP300 downregulates CD20 in diffuse large B-cell lymphoma cells and impairs the cytotoxic effects of anti-CD20 antibodies. Exp Hematol. 2019;79:35–46.PubMed
102.
Roberts CW, Orkin SH. The SWI/SNF complex–chromatin and cancer. Nat Rev Cancer. 2004;4(2):133–42.PubMed
103.
Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, Crabtree GR. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet. 2013;45(6):592–601.PubMedPubMedCentral
104.
Balinas-Gavira C, Rodriguez MI, Andrades A, Cuadros M, Alvarez-Perez JC, Alvarez-Prado AF, de Yebenes VG, Sanchez-Hernandez S, Fernandez-Vigo E, Munoz J, et al. Frequent mutations in the amino-terminal domain of BCL7A impair its tumor suppressor role in DLBCL. Leukemia. 2020;34(10):2722–35.PubMed
105.
Guan B, Gao M, Wu CH, Wang TL, Shih Ie M. Functional analysis of in-frame indel ARID1A mutations reveals new regulatory mechanisms of its tumor suppressor functions. Neoplasia. 2012;14(10):986–93.PubMedPubMedCentral
106.
Shen R, Xu PP, Wang N, Yi HM, Dong L, Fu D, Huang JY, Huang HY, Janin A, Cheng S, et al. Influence of oncogenic mutations and tumor microenvironment alterations on extranodal invasion in diffuse large B-cell lymphoma. Clin Transl Med. 2020;10(7):e221.PubMedPubMedCentral
107.
Helming KC, Wang X, Wilson BG, Vazquez F, Haswell JR, Manchester HE, Kim Y, Kryukov GV, Ghandi M, Aguirre AJ, et al. ARID1B is a specific vulnerability in ARID1A-mutant cancers. Nat Med. 2014;20(3):251–4.PubMedPubMedCentral
108.
Komeno Y, Huang YJ, Qiu J, Lin L, Xu Y, Zhou Y, Chen L, Monterroza DD, Li H, DeKelver RC, et al. SRSF2 is essential for hematopoiesis, and its myelodysplastic syndrome-related mutations dysregulate alternative Pre-mRNA splicing. Mol Cell Biol. 2015;35(17):3071–82.PubMedPubMedCentral
109.
Kon A, Yamazaki S, Nannya Y, Kataoka K, Ota Y, Nakagawa MM, Yoshida K, Shiozawa Y, Morita M, Yoshizato T, et al. Physiological Srsf2 P95H expression causes impaired hematopoietic stem cell functions and aberrant RNA splicing in mice. Blood. 2018;131(6):621–35.PubMedPubMedCentral
110.
Havranek O, Xu J, Kohrer S, Wang Z, Becker L, Comer JM, Henderson J, Ma W, Man Chun Ma J, Westin JR, et al. Tonic B-cell receptor signaling in diffuse large B-cell lymphoma. Blood. 2017;130(8):995–1006.PubMedPubMedCentral
111.
Kober-Hasslacher M, Schmidt-Supprian M. The unsolved puzzle of c-Rel in B cell lymphoma. Cancers (Basel) 2019, 11(7).
112.
Houldsworth J, Mathew S, Rao PH, Dyomina K, Louie DC, Parsa N, Offit K, Chaganti RS. REL proto-oncogene is frequently amplified in extranodal diffuse large cell lymphoma. Blood. 1996;87(1):25–9.PubMed
113.
Feuerhake F, Kutok JL, Monti S, Chen W, LaCasce AS, Cattoretti G, Kurtin P, Pinkus GS, de Leval L, Harris NL, et al. NFkappaB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes. Blood. 2005;106(4):1392–9.PubMed
114.
Houldsworth J, Olshen AB, Cattoretti G, Donnelly GB, Teruya-Feldstein J, Qin J, Palanisamy N, Shen Y, Dyomina K, Petlakh M, et al. Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomas. Blood. 2004;103(5):1862–8.PubMed
115.
Li L, Xu-Monette ZY, Ok CY, Tzankov A, Manyam GC, Sun R, Visco C, Zhang M, Montes-Moreno S, Dybkaer K, et al. Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma. Oncotarget. 2015;6(27):23157–80.PubMedPubMedCentral
116.
Young RM, Staudt LM. Targeting pathological B cell receptor signalling in lymphoid malignancies. Nat Rev Drug Discov. 2013;12(3):229–43.PubMedPubMedCentral
117.
Pfeifer M, Grau M, Lenze D, Wenzel SS, Wolf A, Wollert-Wulf B, Dietze K, Nogai H, Storek B, Madle H, et al. PTEN loss defines a PI3K/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma. Proc Natl Acad Sci USA. 2013;110(30):12420–5.PubMedPubMedCentral
118.
Morris R, Kershaw NJ, Babon JJ. The molecular details of cytokine signaling via the JAK/STAT pathway. Protein Sci. 2018;27(12):1984–2009.PubMedPubMedCentral
119.
Aittomäki S, Pesu M. Therapeutic targeting of the Jak_STAT pathway. Basic Clin Pharmacol Toxicol. 2014;114:18–23.PubMed
120.
Ritz O, Guiter C, Dorsch K, Dusanter-Fourt I, Wegener S, Jouault H, Gaulard P, Castellano F, Moller P, Leroy K. STAT6 activity is regulated by SOCS-1 and modulates BCL-XL expression in primary mediastinal B-cell lymphoma. Leukemia. 2008;22(11):2106–10.PubMed
121.
Ritz O, Rommel K, Dorsch K, Kelsch E, Melzner J, Buck M, Leroy K, Papadopoulou V, Wagner S, Marienfeld R, et al. STAT6-mediated BCL6 repression in primary mediastinal B-cell lymphoma (PMBL). Oncotarget. 2013;4(7):1093–102.PubMedPubMedCentral
122.
Yildiz M, Li H, Bernard D, Amin NA, Ouillette P, Jones S, Saiya-Cork K, Parkin B, Jacobi K, Shedden K, et al. Activating STAT6 mutations in follicular lymphoma. Blood. 2015;125(4):668–79.PubMedPubMedCentral
123.
Xu-Monette ZY, Medeiros LJ, Li Y, Orlowski RZ, Andreeff M, Bueso-Ramos CE, Greiner TC, McDonnell TJ, Young KH. Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies. Blood. 2012;119(16):3668–83.PubMedPubMedCentral
124.
Xu-Monette ZY, Wu L, Visco C, Tai YC, Tzankov A, Liu WM, Montes-Moreno S, Dybkaer K, Chiu A, Orazi A, et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL rituximab-CHOP Consortium Program Study. Blood. 2012;120(19):3986–96.PubMedPubMedCentral
125.
Gebauer N, Bernard V, Gebauer W, Thorns C, Feller AC, Merz H. TP53 mutations are frequent events in double-hit B-cell lymphomas with MYC and BCL2 but not MYC and BCL6 translocations. Leuk Lymphoma. 2015;56(1):179–85.PubMed
126.
Gaidarenko O, Xu Y. Transcription activity is required for p53-dependent tumor suppression. Oncogene. 2009;28(49):4397–401.PubMedPubMedCentral
127.
Song JY, Perry AM, Herrera AF, Chen L, Skrabek P, Nasr MR, Ottesen RA, Nikowitz J, Bedell V, Murata-Collins J, et al. Double-hit signature with TP53 abnormalities predicts poor survival in patients with germinal center type diffuse large B-cell lymphoma treated with R-CHOP. Clin Cancer Res. 2021;27(6):1671–80.PubMedPubMedCentral
128.
Morin RD, Mungall K, Pleasance E, Mungall AJ, Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, et al. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood. 2013;122(7):1256–65.PubMedPubMedCentral
129.
Nairismagi ML, Tan J, Lim JQ, Nagarajan S, Ng CC, Rajasegaran V, Huang D, Lim WK, Laurensia Y, Wijaya GC, et al. JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma. Leukemia. 2016;30(6):1311–9.PubMedPubMedCentral
130.
Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, Wright G, Shaffer AL, Hodson DJ, Buras E, et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012;490(7418):116–20.PubMedPubMedCentral
131.
Jiang L, Gu ZH, Yan ZX, Zhao X, Xie YY, Zhang ZG, Pan CM, Hu Y, Cai CP, Dong Y, et al. Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma. Nat Genet. 2015;47(9):1061–6.PubMed
132.
Hondares E, Brown MA, Musset B, Morgan D, Cherny VV, Taubert C, Bhamrah MK, Coe D, Marelli-Berg F, Gribben JG, et al. Enhanced activation of an amino-terminally truncated isoform of the voltage-gated proton channel HVCN1 enriched in malignant B cells. Proc Natl Acad Sci USA. 2014;111(50):18078–83.PubMedPubMedCentral
133.
Mintz MA, Felce JH, Chou MY, Mayya V, Xu Y, Shui JW, An J, Li Z, Marson A, Okada T, et al. The HVEM-BTLA Axis Restrains T Cell Help to Germinal Center B Cells and Functions as a Cell-Extrinsic Suppressor in Lymphomagenesis. Immunity. 2019;51(2):310–23.PubMedPubMedCentral
134.
Boice M, Salloum D, Mourcin F, Sanghvi V, Amin R, Oricchio E, Jiang M, Mottok A, Denis-Lagache N, Ciriello G, et al. Loss of the HVEM tumor suppressor in lymphoma and restoration by modified CAR-T cells. Cell. 2016;167(2):405–18.PubMedPubMedCentral
135.
Costello RT, Mallet F, Barbarat B, De Colella JMS, Sainty D, Sweet RW, Truneh A, Olive D. Stimulation of non-Hodgkin’s lymphoma via HVEM: an alternate and safe way to increase Fas-induced apoptosis and improve tumor immunogenicity. Leukemia. 2003;17(12):2500–7.PubMed
136.
Green JA, Suzuki K, Cho B, Willison LD, Palmer D, Allen CD, Schmidt TH, Xu Y, Proia RL, Coughlin SR, et al. The sphingosine 1-phosphate receptor S1P(2) maintains the homeostasis of germinal center B cells and promotes niche confinement. Nat Immunol. 2011;12(7):672–80.PubMedPubMedCentral
137.
Muppidi JR, Schmitz R, Green JA, Xiao W, Larsen AB, Braun SE, An J, Xu Y, Rosenwald A, Ott G, et al. Loss of signalling via Galpha13 in germinal centre B-cell-derived lymphoma. Nature. 2014;516(7530):254–8.PubMedPubMedCentral
138.
Cattoretti G, Mandelbaum J, Lee N, Chaves AH, Mahler AM, Chadburn A, Dalla-Favera R, Pasqualucci L, MacLennan AJ. Targeted disruption of the S1P2 sphingosine 1-phosphate receptor gene leads to diffuse large B-cell lymphoma formation. Cancer Res. 2009;69(22):8686–92.PubMedPubMedCentral
139.
Stelling A, Hashwah H, Bertram K, Manz MG, Tzankov A, Muller A. The tumor suppressive TGF-beta/SMAD1/S1PR2 signaling axis is recurrently inactivated in diffuse large B-cell lymphoma. Blood. 2018;131(20):2235–46.PubMed
140.
Xia Z, Zhang X, Liu P, Zhang R, Huang Z, Li D, Xiao X, Wu M, Ning N, Zhang Q, et al. GNA13 regulates BCL2 expression and the sensitivity of GCB-DLBCL cells to BCL2 inhibitors in a palmitoylation-dependent manner. Cell Death Dis. 2021;12(1):54.PubMedPubMedCentral
141.
Zhang J, Weng Z, Huang Y, Li M, Wang F, Wang Y, Rao H. High-grade B-Cell Lymphoma With MYC, BCL2, and/or BCL6 translocations/rearrangements: clinicopathologic features of 51 cases in a single Institution of South China. Am J Surg Pathol. 2020;44(12):1602–11.PubMed
142.
Magistroni V, Mauri M, D’Aliberti D, Mezzatesta C, Crespiatico I, Nava M, Fontana D, Sharma N, Parker W, Schreiber A, et al. De novo UBE2A mutations are recurrently acquired during chronic myeloid leukemia progression and interfere with myeloid differentiation pathways. Haematologica. 2019;104(9):1789–97.PubMedPubMedCentral
143.
Mlynarczyk C, Fontan L, Melnick A. Germinal center-derived lymphomas: the darkest side of humoral immunity. Immunol Rev. 2019;288(1):214–39.PubMedPubMedCentral
144.
Laidlaw BJ, Cyster JG. Transcriptional regulation of memory B cell differentiation. Nat Rev Immunol. 2021;21(4):209–20.PubMed
145.
Hart GT, Wang X, Hogquist KA, Jameson SC. Kruppel-like factor 2 (KLF2) regulates B-cell reactivity, subset differentiation, and trafficking molecule expression. Proc Natl Acad Sci U S A. 2011;108(2):716–21.PubMed
146.
Bonetti P, Testoni M, Scandurra M, Ponzoni M, Piva R, Mensah AA, Rinaldi A, Kwee I, Tibiletti MG, Iqbal J, et al. Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma. Blood. 2013;122(13):2233–41.PubMed
147.
Priebe V, Sartori G, Napoli S, Chung EYL, Cascione L, Kwee I, Arribas AJ, Mensah AA, Rinaldi A, Ponzoni M et al. Role of ETS1 in the transcriptional network of diffuse large B Cell lymphoma of the activated B cell-like type. Cancers (Basel) 2020, 12(7).
148.
Li J, Riedt T, Goossens S, Carrillo Garcia C, Szczepanski S, Brandes M, Pieters T, Dobrosch L, Gutgemann I, Farla N, et al. The EMT transcription factor Zeb2 controls adult murine hematopoietic differentiation by regulating cytokine signaling. Blood. 2017;129(4):460–72.PubMed
149.
Phelan JD, Young RM, Webster DE, Roulland S, Wright GW, Kasbekar M, Shaffer AL 3rd, Ceribelli M, Wang JQ, Schmitz R, et al. A multiprotein supercomplex controlling oncogenic signalling in lymphoma. Nature. 2018;560(7718):387–91.PubMedPubMedCentral
150.
Kim SW, Ramasamy K, Bouamar H, Lin AP, Jiang D, Aguiar RC. MicroRNAs miR-125a and miR-125b constitutively activate the NF-kappaB pathway by targeting the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20). Proc Natl Acad Sci USA. 2012;109(20):7865–70.PubMedPubMedCentral
151.
Mei ZZ, Chen XY, Hu SW, Wang N, Ou XL, Wang J, Luo HH, Liu J, Jiang Y. Kelch-like protein 21 (KLHL21) targets IkappaB kinase-beta to regulate nuclear factor kappa-light chain enhancer of activated B cells (NF-kappaB) signaling negatively. J Biol Chem. 2016;291(35):18176–89.PubMedPubMedCentral
152.
Courtheoux T, Enchev RI, Lampert F, Gerez J, Beck J, Picotti P, Sumara I, Peter M. Cortical dynamics during cell motility are regulated by CRL3(KLHL21) E3 ubiquitin ligase. Nat Commun. 2016;7:12810.PubMedPubMedCentral
153.
Li L, Zhang W, Liu Y, Liu X, Cai L, Kang J, Zhang Y, Chen W, Dong C, Zhang Y, et al. The CRL3(BTBD9) E3 ubiquitin ligase complex targets TNFAIP1 for degradation to suppress cancer cell migration. Signal Transduct Target Ther. 2020;5(1):42.PubMedPubMedCentral
154.
Shanmugam V, Craig JW, Hilton LK, Nguyen MH, Rushton CK, Fahimdanesh K, Lovitch S, Ferland B, Scott DW, Aster JC. Notch activation is pervasive in SMZL and uncommon in DLBCL: implications for Notch signaling in B-cell tumors. Blood Adv. 2021;5(1):71–83.PubMedPubMedCentral
155.
Saito T, Chiba S, Ichikawa M, Kunisato A, Asai T, Shimizu K, Yamaguchi T, Yamamoto G, Seo S, Kumano K, et al. Notch2 Is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development. Immunity. 2003;18(5):675–85.PubMed
156.
Lee SY, Kumano K, Nakazaki K, Sanada M, Matsumoto A, Yamamoto G, Nannya Y, Suzuki R, Ota S, Ota Y, et al. Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma. Cancer Sci. 2009;100(5):920–6.PubMed
157.
Zhang X, Shi Y, Weng Y, Lai Q, Luo T, Zhao J, Ren G, Li W, Pan H, Ke Y, et al. The truncate mutation of Notch2 enhances cell proliferation through activating the NF-kappaB signal pathway in the diffuse large B-cell lymphomas. PLoS ONE. 2014;9(10):e108747.PubMedPubMedCentral
158.
de Miranda NF, Georgiou K, Chen L, Wu C, Gao Z, Zaravinos A, Lisboa S, Enblad G, Teixeira MR, Zeng Y, et al. Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients. Blood. 2014;124(16):2544–53.PubMedPubMedCentral
159.
Meriranta L, Pasanen A, Louhimo R, Cervera A, Alkodsi A, Autio M, Taskinen M, Rantanen V, Karjalainen-Lindsberg ML, Holte H, et al. Deltex-1 mutations predict poor survival in diffuse large B-cell lymphoma. Haematologica. 2017;102(5):e195–8.PubMedPubMedCentral
160.
Filipits M, Jaeger U, Pohl G, Stranzl T, Simonitsch I, Kaider A, Skrabs C, Pirker R. Cyclin D3 is a predictive and prognostic factor in diffuse large B-cell lymphoma. Clin Cancer Res. 2002;8(3):729–33.PubMed
161.
Kim WY, Sharpless NE. The regulation of INK4/ARF in cancer and aging. Cell. 2006;127(2):265–75.PubMed
162.
Kannengiesser C, Brookes S, del Arroyo AG, Pham D, Bombled J, Barrois M, Mauffret O, Avril MF, Chompret A, Lenoir GM, et al. Functional, structural, and genetic evaluation of 20 CDKN2A germ line mutations identified in melanoma-prone families or patients. Hum Mutat. 2009;30(4):564–74.PubMed
163.
Jethwa A, Slabicki M, Hullein J, Jentzsch M, Dalal V, Rabe S, Wagner L, Walther T, Klapper W, Project MN et al. TRRAP is essential for regulating the accumulation of mutant and wild-type p53 in lymphoma. Blood 2018; 131(25):2789–2802.
164.
Xu-Monette ZY, Zhang S, Li X, Manyam GC, Wang XX, Xia Y, Visco C, Tzankov A, Zhang L, Montes-Moreno S, et al. p63 expression confers significantly better survival outcomes in high-risk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function. Aging. 2016;8(2):345–65.PubMedPubMedCentral
165.
Scott DW, Mungall KL, Ben-Neriah S, Rogic S, Morin RD, Slack GW, Tan KL, Chan FC, Lim RS, Connors JM, et al. TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma. Blood. 2012;119(21):4949–52.PubMedPubMedCentral
166.
167.
de Oliveira JF, do Prado PFV, da Costa SS, Sforca ML, Canateli C, Ranzani AT, Maschietto M, de Oliveira PSL, Otto PA, Klevit RE, et al. Mechanistic insights revealed by a UBE2A mutation linked to intellectual disability. Nat Chem Biol. 2019;15(1):62–70.PubMed
168.
Brunet M, Vargas C, Larrieu D, Torrisani J, Dufresne M: E3 ubiquitin ligase TRIP12: regulation, structure, and physiopathological functions. Int J Mol Sci 2020, 21(22).
169.
Jacobs J, Deschoolmeester V, Zwaenepoel K, Rolfo C, Silence K, Rottey S, Lardon F, Smits E, Pauwels P. CD70: an emerging target in cancer immunotherapy. Pharmacol Ther. 2015;155:1–10.PubMed
170.
Bertrand P, Maingonnat C, Penther D, Guney S, Ruminy P, Picquenot JM, Mareschal S, Alcantara M, Bouzelfen A, Dubois S, et al. The costimulatory molecule CD70 is regulated by distinct molecular mechanisms and is associated with overall survival in diffuse large B-cell lymphoma. Genes Chromosom Cancer. 2013;52(8):764–74.PubMed
171.
Challa-Malladi M, Lieu YK, Califano O, Holmes AB, Bhagat G, Murty VV, Dominguez-Sola D, Pasqualucci L, Dalla-Favera R. Combined genetic inactivation of beta2-microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell. 2011;20(6):728–40.PubMedPubMedCentral
172.
Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375(9):819–29.PubMedPubMedCentral
173.
Georgiou K, Chen L, Berglund M, Ren W, de Miranda NF, Lisboa S, Fangazio M, Zhu S, Hou Y, Wu K, et al. Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas. Blood. 2016;127(24):3026–34.PubMed
174.
Song MK, Park BB, Uhm J. Understanding immune evasion and therapeutic targeting associated with PD-1/PD-L1 pathway in diffuse large B-cell lymphoma. Int J Mol Sci 2019, 20(6).
175.
Zabel BA, Lewen S, Berahovich RD, Jaen JC, Schall TJ. The novel chemokine receptor CXCR7 regulates trans-endothelial migration of cancer cells. Mol Cancer. 2011;10:73.PubMedPubMedCentral
176.
Pansy K, Feichtinger J, Ehall B, Uhl B, Sedej M, Roula D, Pursche B, Wolf A, Zoidl M, Steinbauer E et al. The CXCR4-CXCL12-axis is of prognostic relevance in DLBCL and Its antagonists exert pro-apoptotic effects in vitro. Int J Mol Sci 2019, 20(19).
177.
Moreno MJ, Bosch R, Dieguez-Gonzalez R, Novelli S, Mozos A, Gallardo A, Pavon MA, Cespedes MV, Granena A, Alcoceba M, et al. CXCR4 expression enhances diffuse large B cell lymphoma dissemination and decreases patient survival. J Pathol. 2015;235(3):445–55.PubMed
178.
Durr C, Pfeifer D, Claus R, Schmitt-Graeff A, Gerlach UV, Graeser R, Kruger S, Gerbitz A, Negrin RS, Finke J, et al. CXCL12 mediates immunosuppression in the lymphoma microenvironment after allogeneic transplantation of hematopoietic cells. Cancer Res. 2010;70(24):10170–81.PubMed
179.
Peled A, Klein S, Beider K, Burger JA, Abraham M. Role of CXCL12 and CXCR4 in the pathogenesis of hematological malignancies. Cytokine. 2018;109:11–6.PubMed
180.
Kim JH, Kim WS, Ryu KJ, Kim SJ, Park C. CXCR4 can induce PI3Kdelta inhibitor resistance in ABC DLBCL. Blood Cancer J. 2018;8(2):23.PubMedPubMedCentral
181.
Treon SP, Xu L, Guerrera ML, Jimenez C, Hunter ZR, Liu X, Demos M, Gustine J, Chan G, Munshi M, et al. Genomic landscape of waldenstrom macroglobulinemia and its impact on treatment strategies. J Clin Oncol Off J Am Soc Clin Oncol. 2020;38(11):1198–208.
182.
Ennishi D, Healy S, Bashashati A, Saberi S, Hother C, Mottok A, Chan FC, Chong L, Abraham L, Kridel R, et al. TMEM30A loss-of-function mutations drive lymphomagenesis and confer therapeutically exploitable vulnerability in B-cell lymphoma. Nat Med. 2020;26(4):577–88.PubMedPubMedCentral
183.
Drygin D, Lin A, Bliesath J, Ho CB, O’Brien SE, Proffitt C, Omori M, Haddach M, Schwaebe MK, Siddiqui-Jain A, et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res. 2011;71(4):1418–30.PubMed
184.
Webb MS, Tortora N, Cremese M, Kozlowska H, Blaquiere M, Devine DV, Kornbrust DJ. Toxicity and toxicokinetics of a phosphorothioate oligonucleotide against the c-myc oncogene in cynomolgus monkeys. Antisense Nucleic Acid Drug Dev. 2001;11(3):155–63.PubMed
185.
Davids MS, Roberts AW, Seymour JF, Pagel JM, Kahl BS, Wierda WG, Puvvada S, Kipps TJ, Anderson MA, Salem AH, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-hodgkin lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35(8):826–33.
186.
de Vos S, Swinnen LJ, Wang D, Reid E, Fowler N, Cordero J, Dunbar M, Enschede SH, Nolan C, Petrich AM, et al. Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study. Ann Oncol. 2018;29(9):1932–8.PubMedPubMedCentral
187.
Morschhauser F, Feugier P, Flinn IW, Gasiorowski R, Greil R, Illes A, Johnson NA, Larouche JF, Lugtenburg PJ, Patti C, et al. A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma. Blood. 2021;137(5):600–9.PubMedPubMedCentral
188.
Bojarczuk K, Wienand K, Ryan JA, Chen L, Villalobos-Ortiz M, Mandato E, Stachura J, Letai A, Lawton LN, Chapuy B, et al. Targeted inhibition of PI3Kalpha/delta is synergistic with BCL2 blockade in genetically defined subtypes of DLBCL. Blood. 2019;133(1):70–80.PubMedPubMedCentral
189.
Sasi BK, Martines C, Xerxa E, Porro F, Kalkan H, Fazio R, Turkalj S, Bojnik E, Pyrzynska B, Stachura J, et al. Inhibition of SYK or BTK augments venetoclax sensitivity in SHP1-negative/BCL2-positive diffuse large B-cell lymphoma. Leukemia. 2019;33(10):2416–28.PubMed
190.
Scholze H, Stephenson RE, Reynolds R, Shah S, Puri R, Butler SD, Trujillo-Alonso V, Teater MR, van Besien H, Gibbs-Curtis D, et al. Combined EZH2 and BCL2 inhibitors as precision therapy for genetically defined DLBCL subtypes. Blood Adv. 2020;4(20):5226–31.PubMedPubMedCentral
191.
Runckel K, Barth MJ, Mavis C, Gu JJ, Hernandez-Ilizaliturri FJ. The SMAC mimetic LCL-161 displays antitumor activity in preclinical models of rituximab-resistant B-cell lymphoma. Blood Adv. 2018;2(23):3516–25.PubMedPubMedCentral
192.
Cheng C, Wang T, Song Z, Peng L, Gao M, Hermine O, Rousseaux S, Khochbin S, Mi JQ, Wang J. Induction of autophagy and autophagy-dependent apoptosis in diffuse large B-cell lymphoma by a new antimalarial artemisinin derivative, SM1044. Cancer Med. 2018;7(2):380–96.PubMed
193.
Italiano A, Soria JC, Toulmonde M, Michot JM, Lucchesi C, Varga A, Coindre JM, Blakemore SJ, Clawson A, Suttle B, et al. Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study. Lancet Oncol. 2018;19(5):649–59.PubMed
194.
Salles G, Adib D, Navia SB, Rajarethinam A, Whalen J, Radford J, Opat S, McKay P, Jurczak W, Gandhi Laurent D, et al. Phase 2 multicenter study of tazemetostat, an EZH2 inhibitor, in patients with relapsed or refractory follicular lymphoma. Blood. 2019;134(Supp 1):123–123.
195.
Pagel J, Morschhauser F, Herve T, Chaidos A, Phillips T, Ribrag V, Campbell P, Fruchart C, Jurczak W, McKay P, et al. Interim update from a phase 2 multicenter study of tazemetostat, an EZH2 Inhibitor, in patients with relapsed or refractory (R/R) follicular lymphoma (FL). Clin Lymphoma Myeloma Leuk. 2018;18:S278–9.
196.
Honma D, Kanno O, Watanabe J, Kinoshita J, Hirasawa M, Nosaka E, Shiroishi M, Takizawa T, Yasumatsu I, Horiuchi T, et al. Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor. Cancer Sci. 2017;108(10):2069–78.PubMedPubMedCentral
197.
Harb W, Abramson J, Lunning M, Goy A, Maddocks K, Lebedinsky C, Senderowicz A, Trojer P, Bradley WD, Flinn I. A phase 1 study of CPI-1205, a small molecule inhibitor of EZH2, preliminary safety in patients with B-cell lymphomas. Ann Oncol. 2018;29:7.
198.
Ogura M. Corrigenda. Br J Haematol. 2014;166(4):629–629.
199.
Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, et al. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016;128(2):185–94.PubMedPubMedCentral
200.
Guan X-W, Hua-Qing W, Jia L, Liu F-T. The novel HDAC inhibitor chidamide synergizes with rituximab to inhibit DLBCL tumor growth in vitro and in vivo by up-regulating CD20 expression. Blood. 2018;132(Supplement 1):2947–2947.
201.
Lue JK, Prabhu SA, Liu Y, Gonzalez Y, Verma A, Mundi PS, Abshiru N, Camarillo JM, Mehta S, Chen EI, et al. Precision targeting with EZH2 and HDAC inhibitors in epigenetically dysregulated lymphomas. Clin Cancer Res. 2019;25(17):5271–83.PubMedPubMedCentral
202.
Batlevi CL, Crump M, Andreadis C, Rizzieri D, Assouline SE, Fox S, van der Jagt RHC, Copeland A, Potvin D, Chao R, et al. A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma. Br J Haematol. 2017;178(3):434–41.PubMedPubMedCentral
203.
Younes A, Berdeja JG, Patel MR, Flinn I, Gerecitano JF, Neelapu SS, Kelly KR, Copeland AR, Akins A, Clancy MS, et al. Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial. Lancet Oncol. 2016;17(5):622–31.PubMedPubMedCentral
204.
Amorim S, Stathis A, Gleeson M, Iyengar S, Magarotto V, Leleu X, Morschhauser F, Karlin L, Broussais F, Rezai K, et al. Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study. Lancet Haematol. 2016;3(4):e196-204.PubMed
205.
Esteve-Arenys A, Valero JG, Chamorro-Jorganes A, Gonzalez D, Rodriguez V, Dlouhy I, Salaverria I, Campo E, Colomer D, Martinez A, et al. The BET bromodomain inhibitor CPI203 overcomes resistance to ABT-199 (venetoclax) by downregulation of BFL-1/A1 in in vitro and in vivo models of MYC+/BCL2+ double hit lymphoma. Oncogene. 2018;37(14):1830–44.PubMed
206.
Cummin TEC, Cox KL, Murray TD, Turaj AH, Dunning L, English VL, Fell R, Packham G, Ma Y, Powell B, et al. BET inhibitors synergize with venetoclax to induce apoptosis in MYC-driven lymphomas with high BCL2 expression. Blood Adv. 2020;4(14):3316–28.PubMedPubMedCentral
207.
Abramson JS, Blum KA, Flinn IW, Gutierrez M, Goy A, Maris M, Cooper M, O’Meara M, Borger D, Mertz J, et al. BET inhibitor CPI-0610 is well tolerated and induces responses in diffuse large B-cell lymphoma and follicular lymphoma: preliminary analysis of an ongoing phase 1 study. Blood. 2015;126(23):1491.
208.
Hogg SJ, Newbold A, Vervoort SJ, Cluse LA, Martin BP, Gregory GP, Lefebure M, Vidacs E, Tothill RW, Bradner JE, et al. BET inhibition induces apoptosis in aggressive B-cell lymphoma via epigenetic regulation of BCL2 family members. Mol Cancer Ther. 2016;15(9):2030–41.PubMed
209.
Martin P, Bartlett NL, Rivera IIR, Revuelta M, Chavez JC, Reagan JL, Smith SM, LaCasce AS, Zhang L, Zhai M, et al. A phase I, open label, multicenter trial of oral azacitidine (CC-486) Plus R-CHOP in patients with high-risk, previously untreated diffuse large B-cell lymphoma, grade 3B follicular lymphoma, or transformed lymphoma. Blood. 2017;130:192.
210.
Magagnoli M, Carlo-Stella C, Santoro A. Copanlisib for the treatment of adults with relapsed follicular lymphoma. Expert Rev Clin Pharmacol. 2020;13(8):813–23.PubMed
211.
Whitfield JR, Beaulieu ME, Soucek L. Strategies to inhibit Myc and their clinical applicability. Front Cell Dev Biol. 2017;5:10.PubMedPubMedCentral
212.
Berg T, Cohen SB, Desharnais J, Sonderegger C, Maslyar DJ, Goldberg J, Boger DL, Vogt PK. Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts. Proc Natl Acad Sci USA. 2002;99(6):3830–5.PubMedPubMedCentral
213.
Chen BJ, Wu YL, Tanaka Y, Zhang W. Small molecules targeting c-Myc oncogene: promising anti-cancer therapeutics. Int J Biol Sci. 2014;10(10):1084–96.PubMedPubMedCentral
214.
Han H, Jain AD, Truica MI, Izquierdo-Ferrer J, Anker JF, Lysy B, Sagar V, Luan Y, Chalmers ZR, Unno K, et al. Small-molecule MYC inhibitors suppress tumor growth and enhance immunotherapy. Cancer cell. 2019;36(5):483–97.PubMedPubMedCentral
215.
Clausen DM, Guo J, Parise RA, Beumer JH, Egorin MJ, Lazo JS, Prochownik EV, Eiseman JL. In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074–G5, a novel small-molecule inhibitor of c-Myc/Max dimerization. J Pharmacol Exp Ther. 2010;335(3):715–27.PubMedPubMedCentral
216.
Wang H, Chauhan J, Hu A, Pendleton K, Yap JL, Sabato PE, Jones JW, Perri M, Yu J, Cione E, Kane MA. Disruption of Myc-Max heterodimerization with improved cell-penetrating analogs of the small molecule 10074–G5. Oncotarget. 2013;4(6):936–49.PubMedPubMedCentral
217.
Mo H, Henriksson M. Identification of small molecules that induce apoptosis in a Myc-dependent manner and inhibit Myc-driven transformation. Proc Natl Acad Sci USA. 2005;103(16):6344–9.
218.
Mo H, Vita M, Crespin M, Henriksson M. Myc overexpression enhances apoptosis induced by small molecules. Cell Cycle. 2006;5(19):2191–4.PubMed
219.
Neidle S. Quadruplex nucleic acids as novel therapeutic targets. J Med Chem. 2016;59:5987–6011.PubMed
220.
Brown ZZ, Mapelli C, Farasat I, Shoultz AV, Johnson SA, Orvieto F, Santoprete A, Bianchi E, McCracken AB, Chen K, et al. Multiple synthetic routes to the mini-protein omomyc and coiled-coil domain truncations. J Org Chem. 2020;85(3):1466–75.PubMed
221.
Masso-Valles D, Soucek L. Blocking Myc to treat cancer: reflecting on two decades of omomyc. Cells. 2020;9(4):883.PubMedCentral
222.
Zhang X, Bi C, Lu T, Zhang W, Yue T, Wang C, Tian T, Zhang X, Huang Y, Lunning M, et al. Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas. Leukemia. 2020;34(1):138–50.PubMed
223.
Chu J, Zhang W, Cencic R, O’Connor PBF, Robert F, Devine WG, Selznick A, Henkel T, Merrick WC, Brown LE, et al. Rocaglates induce gain-of-function alterations to eIF4A and eIF4F. Cell Rep. 2020;30(8):2481–8.PubMedPubMedCentral
224.
Ren Y, Bi C, Zhao X, Lwin T, Wang C, Yuan J, Silva AS, Shah BD, Fang B, Li T, et al. PLK1 stabilizes a MYC-dependent kinase network in aggressive B cell lymphomas. J Clin Invest. 2018;128(12):5517–30.PubMedPubMedCentral
225.
Wang J, Liu Z, Wang Z, Wang S, Chen Z, Li Z, Zhang M, Zou J, Dong B, Gao J, et al. Targeting c-Myc: JQ1 as a promising option for c-Myc-amplified esophageal squamous cell carcinoma. Cancer Lett. 2018;419:64–74.PubMed
226.
Wu Z, Hu Z, Han X, Li Z, Zhu Q, Wang Y, Zheng Q, Yan J. The BET-Bromodomain Inhibitor JQ1 synergized ABT-263 against colorectal cancer cells through suppressing c-Myc-induced miR-1271-5p expression. Biomed Pharmacother. 2017;95:1574–9.PubMed
227.
Devaiah BN, Mu J, Akman B, Uppal S, Weissman JD, Cheng D, Baranello L, Nie Z, Levens D, Singer DS. MYC protein stability is negatively regulated by BRD4. Proc Natl Acad Sci USA. 2020;117(24):13457–67.PubMedPubMedCentral
228.
Zelenetz AD, Salles G, Mason KD, Casulo C, Le Gouill S, Sehn LH, Tilly H, Cartron G, Chamuleau MED, Goy A, et al. Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: results from the CAVALLI phase 1b trial. Blood. 2019;133(18):1964–76.PubMedPubMedCentral
229.
O’Steen S, Green DJ, Gopal AK, Orozco JJ, Kenoyer AL, Lin Y, Wilbur DS, Hamlin DK, Fisher DR, Hylarides MD, et al. Venetoclax synergizes with radiotherapy for treatment of B-cell lymphomas. Cancer Res. 2017;77(14):3885–93.PubMedPubMedCentral
230.
Copie-Bergman C. Double-hit DLBCL: should we limit FISH testing? Blood. 2018;131(18):1997–8.PubMed
231.
Pham LV, Huang S, Zhang H, Zhang J, Bell T, Zhou S, Pogue E, Ding Z, Lam L, Westin J, et al. Strategic therapeutic targeting to overcome venetoclax resistance in aggressive b-cell lymphomas. Clin Cancer Res. 2018;24(16):3967–80.PubMed
232.
Yecies D, Carlson NE, Deng J, Letai A. Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1. Blood. 2010;115(16):3304–13.PubMedPubMedCentral
233.
Haselager MV, Kielbassa K, Ter Burg J, Bax DJC, Fernandes SM, Borst J, Tam C, Forconi F, Chiodin G, Brown JR, et al. Changes in BCL2 members after ibrutinib or venetoclax uncover functional hierarchy in determining resistance to venetoclax in CLL. Blood. 2020;136(25):2918–26.PubMed
234.
Li L, Pongtornpipat P, Tiutan T, Kendrick SL, Park S, Persky DO, Rimsza LM, Puvvada SD, Schatz JH. Synergistic induction of apoptosis in high-risk DLBCL by BCL2 inhibition with ABT-199 combined with pharmacologic loss of MCL1. Leukemia. 2015;29(8):1702–12.PubMedPubMedCentral
235.
Klanova M, Andera L, Brazina J, Svadlenka J, Benesova S, Soukup J, Prukova D, Vejmelkova D, Jaksa R, Helman K, et al. Targeting of BCL2 Family Proteins with ABT-199 and Homoharringtonine Reveals BCL2- and MCL1-Dependent Subgroups of Diffuse Large B-Cell Lymphoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2016;22(5):1138–49.
236.
Caenepeel S, Brown SP, Belmontes B, Moody G, Keegan KS, Chui D, Whittington DA, Huang X, Poppe L, Cheng AC, et al. AMG 176, a selective MCL1 inhibitor, is effective in hematologic cancer models alone and in combination with established therapies. Cancer Discov. 2018;8(12):1582–97.PubMed
237.
Michie J, Kearney CJ, Hawkins ED, Silke J, Oliaro J. The immuno-modulatory effects of inhibitor of apoptosis protein antagonists in cancer immunotherapy. Cells. 2020;9(1):207.PubMedCentral
238.
Wu G, Chai J, Suber TL, Wu JW, Du C, Wang X, Shi Y. Structural basis of IAP recognition by Smac/DIABLO. Nature. 2000;408:1008–12.PubMed
239.
Condon SM, Mitsuuchi Y, Deng Y, LaPorte MG, Rippin SR, Haimowitz T, Alexander MD, Kumar PT, Hendi MS, Lee YH, et al. Birinapant, a smac-mimetic with improved tolerability for the treatment of solid tumors and hematological malignancies. J Med Chem. 2014;57(9):3666–77.PubMed
240.
Cong H, Xu L, Wu Y, Qu Z, Bian T, Zhang W, Xing C, Zhuang C. Inhibitor of Apoptosis Protein (IAP) antagonists in anticancer agent discovery: current status and perspectives. J Med Chem. 2019;62(12):5750–72.PubMed
241.
Perry AM, Mitrovic Z, Chan WC. Biological prognostic markers in diffuse large B-cell lymphoma.pdf. Cancer Control. 2012;19:214–26.PubMed
242.
Rauch A, Hennig D, Schafer C, Wirth M, Marx C, Heinzel T, Schneider G, Kramer OH. Survivin and YM155: How faithful is the liaison? Biochim Biophys Acta. 2014;1845(2):202–20.PubMed
243.
Kita A, Mitsuoka K, Kaneko N, Nakata M, Yamanaka K, Jitsuoka M, Miyoshi S, Noda A, Mori M, Nakahara T, et al. Sepantronium bromide (YM155) enhances response of human B-cell non-Hodgkin lymphoma to rituximab. J Pharmacol Exp Ther. 2012;343(1):178–83.PubMed
244.
Kaneko N, Mitsuoka K, Amino N, Yamanaka K, Kita A, Mori M, Miyoshi S, Kuromitsu S. Combination of YM155, a survivin suppressant, with bendamustine and rituximab: a new combination therapy to treat relapsed/refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2014;20(7):1814–22.PubMed
245.
Cai Q, Sun H, Peng Y, Lu J, Nikolovska-Coleska Z, McEachern D, Liu L, Qiu S, Yang CY, Miller R, et al. A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment. J Med Chem. 2011;54(8):2714–26.PubMedPubMedCentral
246.
DiPersio JF, Erba HP, Larson RA, Luger SM, Tallman MS, Brill JM, Vuagniaux G, Rouits E, Sorensen JM, Zanna C. Oral Debio1143 (AT406), an antagonist of inhibitor of apoptosis proteins, combined with daunorubicin and cytarabine in patients with poor-risk acute myeloid leukemia–results of a phase I dose-escalation study. Clin Lymphoma Myeloma Leuk. 2015;15(7):443–9.PubMedPubMedCentral
247.
Zinngrebe J, Schlichtig F, Kraus JM, Meyer M, Boldrin E, Kestler HA, Meyer LH, Fischer-Posovszky P, Debatin KM. Biomarker profile for prediction of response to SMAC mimetic monotherapy in pediatric precursor B-cell acute lymphoblastic leukemia. Int J Cancer. 2020;146(11):3219–31.PubMed
248.
Vaque JP, Martinez N, Batlle-Lopez A, Perez C, Montes-Moreno S, Sanchez-Beato M, Piris MA. B-cell lymphoma mutations: improving diagnostics and enabling targeted therapies. Haematologica. 2014;99(2):222–31.PubMedPubMedCentral
249.
Beauchamp E, Yap MC, Iyer A, Perinpanayagam MA, Gamma JM, Vincent KM, Lakshmanan M, Raju A, Tergaonkar V, Tan SY, et al. Targeting N-myristoylation for therapy of B-cell lymphomas. Nat Commun. 2020;11(1):5348.PubMedPubMedCentral
250.
Lv S, Wen H, Shan X, Li J, Wu Y, Yu X, Huang W, Wei Q. Loss of KMT2D induces prostate cancer ROS-mediated DNA damage by suppressing the enhancer activity and DNA binding of antioxidant transcription factor FOXO3. Epigenetics. 2019;14(12):1194–208.PubMedPubMedCentral
251.
Sermer D, Pasqualucci L, Wendel HG, Melnick A, Younes A. Emerging epigenetic-modulating therapies in lymphoma. Nat Rev Clin Oncol. 2019;16(8):494–507.PubMedPubMedCentral
252.
Wang G, Chow RD, Zhu L, Bai Z, Ye L, Zhang F, Renauer PA, Dong MB, Dai X, Zhang X, et al. CRISPR-GEMM pooled mutagenic screening identifies KMT2D as a major modulator of immune checkpoint blockade. Cancer Discov. 2020;10(12):1912–33.PubMedPubMedCentral
253.
Bereshchenko OR, Gu W, Dalla-Favera R. Acetylation inactivates the transcriptional repressor BCL6. Nat Genet. 2002;32(4):606–13.PubMed
254.
Guan XW, Wang HQ, Ban WW, Chang Z, Chen HZ, Jia L, Liu FT. Novel HDAC inhibitor Chidamide synergizes with Rituximab to inhibit diffuse large B-cell lymphoma tumour growth by upregulating CD20. Cell Death Dis. 2020;11(1):20.PubMedPubMedCentral
255.
Wu SY, Chiang CM. The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J Biol Chem. 2007;282(18):13141–5.PubMed
256.
257.
Najafova Z, Tirado-Magallanes R, Subramaniam M, Hossan T, Schmidt G, Nagarajan S, Baumgart SJ, Mishra VK, Bedi U, Hesse E, et al. BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire. Nucleic Acids Res. 2017;45(1):127–41.PubMed
258.
Ozer HG, El-Gamal D, Powell B, Hing ZA, Blachly JS, Harrington B, Mitchell S, Grieselhuber NR, Williams K, Lai TH, et al. BRD4 profiling identifies critical chronic lymphocytic leukemia oncogenic circuits and reveals sensitivity to PLX51107, a novel structurally distinct BET inhibitor. Cancer Discov. 2018;8(4):458–77.PubMedPubMedCentral
259.
Vazquez R, Riveiro ME, Astorgues-Xerri L, Odore E, Rezai K, Erba E, Panini N, Rinaldi A, Kwee I, Beltrame L, et al. The bromodomain inhibitor OTX015 (MK-8628) exerts anti-tumor activity in triple-negative breast cancer models as single agent and in combination with everolimus. Oncotarget. 2017;8(5):7598–613.PubMed
260.
Kurniyati K, Kelly JF, Vinogradov E, Robotham A, Tu Y, Wang J, Liu J, Logan SM, Li C. A novel glycan modifies the flagellar filament proteins of the oral bacterium Treponema denticola. Mol Microbiol. 2017;103(1):67–85.PubMed
261.
Piunti A, Hashizume R, Morgan MA, Bartom ET, Horbinski CM, Marshall SA, Rendleman EJ, Ma Q, Takahashi YH, Woodfin AR, et al. Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas. Nat Med. 2017;23(4):493–500.PubMedPubMedCentral
262.
Li W, Gupta SK, Han W, Kundson RA, Nelson S, Knutson D, Greipp PT, Elsawa SF, Sotomayor EM, Gupta M. Targeting MYC activity in double-hit lymphoma with MYC and BCL2 and/or BCL6 rearrangements with epigenetic bromodomain inhibitors. J Hematol Oncol. 2019;12(1):73.PubMedPubMedCentral
263.
Pfister SX, Ashworth A. Marked for death: targeting epigenetic changes in cancer. Nat Rev Drug Discov. 2017;16(4):241–63.PubMed
264.
Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol. 2007;178(5):2623–9.PubMed
265.
Tamma R, Ingravallo G, Gaudio F, Annese T, Albano F, Ruggieri S, Dicataldo M, Maiorano E, Specchia G, Ribatti D. STAT3, tumor microenvironment, and microvessel density in diffuse large B cell lymphomas. Leuk Lymphoma. 2020;61(3):567–74.PubMed
266.
Zhou H, Bai L, Xu R, Zhao Y, Chen J, McEachern D, Chinnaswamy K, Wen B, Dai L, Kumar P, et al. Structure-based discovery of SD-36 as a potent, selective, and efficacious PROTAC degrader of STAT3 protein. J Med Chem. 2019;62(24):11280–300.PubMedPubMedCentral
267.
Bai L, Zhou H, Xu R, Zhao Y, Chinnaswamy K, McEachern D, Chen J, Yang CY, Liu Z, Wang M, et al. A potent and selective small-molecule degrader of STAT3 achieves complete tumor regression in vivo. Cancer cell. 2019;36(5):498–511.PubMedPubMedCentral
268.
Shastri A, Choudhary G, Teixeira M, Gordon-Mitchell S, Ramachandra N, Bernard L, Bhattacharyya S, Lopez R, Pradhan K, Giricz O, et al. Antisense STAT3 inhibitor decreases viability of myelodysplastic and leukemic stem cells. J Clin Invest. 2018;128(12):5479–88.PubMedPubMedCentral
269.
Reilley MJ, McCoon P, Cook C, Lyne P, Kurzrock R, Kim Y, Woessner R, Younes A, Nemunaitis J, Fowler N, et al. STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: results of a phase 1b trial. J Immunother Cancer. 2018;6(1):119.PubMedPubMedCentral
270.
Hong D, Kurzrock R, Kim Y, Woessner R, Younes A, Nemunaitis J, Fowler N, Zhou T, Schmidt J, Jo M, et al. AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer. Sci Transl Med. 2015;7:314ra185.PubMedPubMedCentral
271.
Furqan M, Mukhi N, Lee B, Liu D. Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application. Biomark Res. 2013;1(1):5.PubMedPubMedCentral
272.
Rancea M, Will A, Borchmann P, Monsef I, Engert A, Skoetz N. Sixteenth biannual report of the Cochrane Haematological Malignancies Group: focus on Non-Hodgkin’s lymphoma. J Natl Cancer Inst. 2014;106(8):dju170.PubMed
273.
Doheny D, Sirkisoon S, Carpenter RL, Aguayo NR, Regua AT, Anguelov M, Manore SG, Arrigo A, Jalboush SA, Wong GL, et al. Combined inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 pathways suppresses breast cancer stem cells, tumor growth, and metastasis. Oncogene. 2020;39(42):6589–605.PubMedPubMedCentral
274.
Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V, Szoke A, Drummond M, Pristupa A, Granston T, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018;4(5):652–9.PubMedPubMedCentral
275.
Vajpayee N, Thakral C, Gopaluni S, Newman N, Gajra A. Activation of mammalian target of rapamycin in diffuse large B-cell lymphoma: a clinicopathological study. Leuk Res. 2012;36(11):1403–9.PubMed
276.
Graf SA, Gopal AK. Idelalisib for the treatment of non-Hodgkin lymphoma. Expert Opin Pharmacother. 2016;17(2):265–74.PubMedPubMedCentral
277.
Kapoor I, Li Y, Sharma A, Zhu H, Bodo J, Xu W, Hsi ED, Hill BT, Almasan A. Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K/AKT activation in B-cell lymphoid malignancies. Cell Death Dis. 2019;10(12):924.PubMedPubMedCentral
278.
Yahiaoui A, Meadows SA, Sorensen RA, Cui ZH, Keegan KS, Brockett R, Chen G, Queva C, Li L, Tannheimer SL. PI3Kdelta inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kdelta and BTK inhibitors. PLoS ONE. 2017;12(2):e017221.
279.
Krause G, Hassenruck F, Hallek M. Copanlisib for treatment of B-cell malignancies: the development of a PI3K inhibitor with considerable differences to idelalisib. Drug Des Devel Ther. 2018;12:2577–90.PubMedPubMedCentral
280.
Ysebaert L, Morschhauser F. Enzastaurin hydrochloride for lymphoma: reassessing the results of clinical trials in light of recent advances in the biology of B-cell malignancies. Expert Opin Investig Drugs. 2011;20(8):1167–74.PubMed
281.
Robertson MJ, Kahl BS, Vose JM, de Vos S, Laughlin M, Flynn PJ, Rowland K, Cruz JC, Goldberg SL, Musib L, et al. Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(13):1741–6.
282.
Civallero M, Cosenza M, Bari A, Sacchi S. Rational combinations of enzastaurin with novel targeted agents for patients with B-cell non-Hodgkin’s lymphoma. Expert Opin Investig Drugs. 2011;20(8):1029–31.PubMed
283.
Petrich AM, Leshchenko V, Kuo PY, Xia B, Thirukonda VK, Ulahannan N, Gordon S, Fazzari MJ, Ye BH, Sparano JA, et al. Akt inhibitors MK-2206 and nelfinavir overcome mTOR inhibitor resistance in diffuse large B-cell lymphoma. Clin Cancer Res. 2012;18(9):2534–44.PubMedPubMedCentral
284.
Wang J, Xu-Monette ZY, Jabbar KJ, Shen Q, Manyam GC, Tzankov A, Visco C, Wang J, Montes-Moreno S, Dybkaer K, et al. AKT hyperactivation and the potential of AKT-targeted therapy in diffuse large B-cell lymphoma. Am J Pathol. 2017;187(8):1700–16.PubMedPubMedCentral
285.
Yee KW, Zeng Z, Konopleva M, Verstovsek S, Ravandi F, Ferrajoli A, Thomas D, Wierda W, Apostolidou E, Albitar M, et al. Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2006;12(17):5165–73.PubMed
286.
Merli M, Ferrario A, Maffioli M, Arcaini L, Passamonti F. Everolimus in diffuse large B-cell lymphomas. Future Oncol. 2015;11(3):373–83.PubMed
287.
Ansell SM, Tang H, Kurtin PJ, Koenig PA, Inwards DJ, Shah K, Ziesmer SC, Feldman AL, Rao R, Gupta M, et al. Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. Lancet Oncol. 2011;12(4):361–8.PubMedPubMedCentral
288.
Zoellner AK, Bayerl S, Hutter G, Zimmermann Y, Hiddemann W, Dreyling M. Temsirolimus inhibits cell growth in combination with inhibitors of the B-cell receptor pathway. Leuk Lymphoma. 2015;56(12):3393–400.PubMed
289.
Shen J, Ju Z, Zhao W, Wang L, Peng Y, Ge Z, Nagel ZD, Zou J, Wang C, Kapoor P, et al. ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade. Nat Med. 2018;24(5):556–62.PubMedPubMedCentral
290.
Meng X, Matlawska-Wasowska K, Girodon F, Mazel T, Willman CL, Atlas S, Chen IM, Harvey RC, Hunger SP, Ness SA, et al. GSI-I (Z-LLNle-CHO) inhibits gamma-secretase and the proteosome to trigger cell death in precursor-B acute lymphoblastic leukemia. Leukemia. 2011;25(7):1135–46.PubMedPubMedCentral
291.
Tohda S, Sato T, Kogoshi H, Fu L, Sakano S, Nara N. Establishment of a novel B-cell lymphoma cell line with suppressed growth by gamma-secretase inhibitors. Leuk Res. 2006;30(11):1385–90.PubMed
292.
Godfrey JK, Nabhan C, Karrison T, Kline JP, Cohen KS, Bishop MR, Stadler WM, Karmali R, Venugopal P, Rapoport AP, et al. Phase 1 study of lenalidomide plus dose-adjusted EPOCH-R in patients with aggressive B-cell lymphomas with deregulated MYC and BCL2. Cancer. 2019;125(11):1830–6.PubMed
293.
Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, et al. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma: a phase II study. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33(3):251–7.
294.
Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, Spina M, Pavone V, Ladetto M, Liberati AM, et al. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014;15(7):730–7.PubMed
295.
Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, et al. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013;27(9):1902–9.PubMed
296.
Goy A, Ramchandren R, Ghosh N, Munoz J, Morgan DS, Dang NH, Knapp M, Delioukina M, Kingsley E, Ping J, et al. Ibrutinib plus lenalidomide and rituximab has promising activity in relapsed/refractory non-germinal center B-cell-like DLBCL. Blood. 2019;134(13):1024–36.PubMedPubMedCentral
297.
Thieblemont C, Tilly H, Gomes da Silva M, Casasnovas RO, Fruchart C, Morschhauser F, Haioun C, Lazarovici J, Grosicka A, Perrot A, et al. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35(22):2473–81.
298.
Jiang L, Sun Y, Wang J, He Q, Chen X, Lan X, Chen J, Dou QP, Shi X, Liu J. Proteasomal cysteine deubiquitinase inhibitor b-AP15 suppresses migration and induces apoptosis in diffuse large B cell lymphoma. J Exp Clin Cancer Res. 2019;38(1):453.PubMedPubMedCentral
299.
Kasamon YL, Price LSL, Okusanya OO, Richardson NC, Li RJ, Ma L, Wu YT, Theoret M, Pazdur R, Gormley NJ. FDA approval summary: selinexor for relapsed or refractory diffuse large B-cell lymphoma. Oncologist. 2021;99:1–12.
300.
Dey J, Deckwerth TL, Kerwin WS, Casalini JR, Merrell AJ, Grenley MO, Burns C, Ditzler SH, Dixon CP, Beirne E, et al. Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk diffuse large B-cell lymphoma to BCL2 inhibition. Sci Rep. 2017;7(1):18007.PubMedPubMedCentral
301.
Liu SH, Gu Y, Pascual B, Yan Z, Hallin M, Zhang C, Fan C, Wang W, Lam J, Spilker ME, et al. A novel CXCR4 antagonist IgG1 antibody (PF-06747143) for the treatment of hematologic malignancies. Blood Adv. 2017;1(15):1088–100.PubMedPubMedCentral
302.
Falgas A, Pallares V, Unzueta U, Nunez Y, Sierra J, Gallardo A, Alba-Castellon L, Mangues MA, Alamo P, Villaverde A, et al. Specific cytotoxic effect of an auristatin nanoconjugate towards CXCR4(+) diffuse large B-cell lymphoma cells. Int J Nanomed. 2021;16:1869–88.
303.
Lapa C, Hanscheid H, Kircher M, Schirbel A, Wunderlich G, Werner RA, Samnick S, Kotzerke J, Einsele H, Buck AK, et al. Feasibility of CXCR4-directed radioligand therapy in advanced diffuse large B-Cell lymphoma. J Nucl Med. 2019;60(1):60–4.PubMed
304.
Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, Millenson MM, Cohen AD, Schuster SJ, Lebovic D, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(23):2698–704.
305.
Ansell SM, Minnema MC, Johnson P, Timmerman JM, Armand P, Shipp MA, Rodig SJ, Ligon AH, Roemer MGM, Reddy N, et al. Nivolumab for relapsed/refractory diffuse large B-cell lymphoma in patients ineligible for or having failed autologous transplantation: a single-arm, phase II study. J Clin Oncol Off J Am Soc Clin Oncol. 2019;37(6):481–9.
306.
Godfrey J, Tumuluru S, Bao R, Leukam M, Venkataraman G, Phillip J, Fitzpatrick C, McElherne J, MacNabb BW, Orlowski R, et al. PD-L1 gene alterations identify a subset of diffuse large B-cell lymphoma harboring a T-cell-inflamed phenotype. Blood. 2019;133(21):2279–90.PubMedPubMedCentral
307.
Smith SD, Till BG, Shadman MS, Lynch RC, Cowan AJ, Wu QV, Voutsinas J, Rasmussen HA, Blue K, Ujjani CS, et al. Pembrolizumab with R-CHOP in previously untreated diffuse large B-cell lymphoma: potential for biomarker driven therapy. Br J Haematol. 2020;189(6):1119–26.PubMed
308.
Gharaibeh L, Elmadany N, Alwosaibai K, Alshaer W. Notch1 in cancer therapy: possible clinical implications and challenges. Mol Pharmacol. 2020;98(5):559–76.PubMed
309.
Chen F, Pisklakova A, Li M, Baz R, Sullivan DM, Nefedova Y. Gamma-secretase inhibitor enhances the cytotoxic effect of bortezomib in multiple myeloma. Cell Oncol (Dordr). 2011;34(6):545–51.
310.
Saltarella I, Frassanito MA, Lamanuzzi A, Brevi A, Leone P, Desantis V, Di Marzo L, Bellone M, Derudas D, Ribatti D, et al. Homotypic and heterotypic activation of the notch pathway in multiple myeloma-enhanced angiogenesis: a novel therapeutic target? Neoplasia. 2019;21(1):93–105.PubMed
311.
Aster JC, Blacklow SC, Pear WS. Notch signalling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignancies. J Pathol. 2011;223(2):262–73.PubMed
312.
Pont MJ, Hill T, Cole GO, Abbott JJ, Kelliher J, Salter AI, Hudecek M, Comstock ML, Rajan A, Patel BKR, et al. gamma-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood. 2019;134(19):1585–97.PubMedPubMedCentral
313.
Fabbro D, Bauer M, Murone M, Lehal R. Notch inhibition in cancer: challenges and opportunities. Chimia (Aarau). 2020;74(10):779–83.
314.
Lehal R, Zaric J, Vigolo M, Urech C, Frismantas V, Zangger N, Cao L, Berger A, Chicote I, Loubery S, et al. Pharmacological disruption of the Notch transcription factor complex. Proc Natl Acad Sci USA. 2020;117(28):16292–301.PubMedPubMedCentral
315.
Miao Y, Medeiros LJ, Li Y, Li J, Young KH. Genetic alterations and their clinical implications in DLBCL. Nat Rev Clin Oncol. 2019;16(10):634–52.PubMed
316.
Karmali R, Gordon LI. Molecular subtyping in diffuse large B cell lymphoma: closer to an approach of precision therapy. Curr Treat Opt Oncol. 2017;18(2):1–17.
317.
Davids MS, Brown JR. Ibrutinib: a first in class covalent inhibitor of Bruton’s tyrosine kinase. Future Oncol. 2014;10(6):957–67.PubMed
318.
Al-Juhaishi T, McKay J, Sindel A, Yazbeck V. Perspectives on chemotherapy for the management of double-hit lymphoma. Expert Opin Pharmacother. 2020;21(6):653–61.PubMed
319.
Suljagic M, Longo PG, Bennardo S, Perlas E, Leone G, Laurenti L, Efremov DG. The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Emu- TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling. Blood. 2010;116(23):4894–905.PubMed
320.
Choi MY, Kipps TJ. Inhibitors of B-cell receptor signaling for patients with B-cell malignancies. Cancer J. 2012;18(5):404–10.PubMedPubMedCentral
321.
Coffey G, Betz A, DeGuzman F, Pak Y, Inagaki M, Baker DC, Hollenbach SJ, Pandey A, Sinha U. The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and B-cell cancer. J Pharmacol Exp Ther. 2014;351(3):538–48.PubMed
322.
Ma J, Xing W, Coffey G, Dresser K, Lu K, Guo A, Raca G, Pandey A, Conley P, Yu H, Wang YL, et al. Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma. Oncotarget. 2015;6(41):43881–96.PubMedPubMedCentral
323.
Chen Y-B, LaCasce AS. Nzastaurin. Expert Opin Investig Drugs. 2008;17:939–44.PubMed
324.
Young RM, Shaffer AL 3rd, Phelan JD, Staudt LM. B-cell receptor signaling in diffuse large B-cell lymphoma. Semin Hematol. 2015;52(2):77–85.PubMedPubMedCentral
325.
Ferch U, Kloo B, Gewies A, Pfander V, Duwel M, Peschel C, Krappmann D, Ruland J. Inhibition of MALT1 protease activity is selectively toxic for activated B cell-like diffuse large B cell lymphoma cells. J Exp Med. 2009;206(11):2313–20.PubMedPubMedCentral
326.
Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, et al. Oncogenically active MYD88 mutations in human lymphoma. Nature. 2011;470(7332):115–9.PubMed
327.
Karmali R, Gordon LI. Molecular subtyping in diffuse large B cell lymphoma: closer to an approach of precision therapy. Curr Treat Options Oncol. 2017;18(2):11.PubMed
328.
Zhang LH, Kosek J, Wang M, Heise C, Schafer PH, Chopra R. Lenalidomide efficacy in activated B-cell-like subtype diffuse large B-cell lymphoma is dependent upon IRF4 and cereblon expression. Br J Haematol. 2013;160(4):487–502.PubMed
329.
Friedberg JW. How I treat double-hit lymphoma. Blood. 2017;130(5):590–6.PubMed
330.
Salati M, Tarantino V, Maiorana A, Bettelli S, Luminari S. Durable remission in a patient with leptomeningeal relapse of a MYC/BCL6-positive double-hit DLBCL treated with lenalidomide monotherapy. Hematol Oncol. 2017;35(4):861–3.PubMed
331.
Zhu M. Inhibitory effects of bortezomib in a subcutaneous tumor model of H22 mouse hepatocarcinoma cells. Pathol Res Pract. 2019;215(6):152388.PubMed
332.
Dunleavy K, Pittaluga S, Czuczman MS, Dave SS, Wright G, Grant N, Shovlin M, Jaffe ES, Janik JE, Staudt LM, et al. Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood. 2009;113(24):6069–76.PubMedPubMedCentral
333.
Cengiz Seval G, Beksac M. The safety of bortezomib for the treatment of multiple myeloma. Expert Opin Drug Saf. 2018;17(9):953–62.PubMed
334.
Yazbeck V, Shafer D, Perkins EB, Coppola D, Sokol L, Richards KL, Shea T, Ruan J, Parekh S, Strair R, et al. A phase II trial of bortezomib and vorinostat in mantle cell lymphoma and diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2018;18(9):569–75.PubMed
335.
Camicia R, Winkler HC, Hassa PO. Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review. Mol Cancer. 2015;14:207.PubMedPubMedCentral
336.
Tian Z, Zhao JJ, Tai YT, Amin SB, Hu Y, Berger AJ, Richardson P, Chauhan D, Anderson KC. Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells. Blood. 2012;120(19):3958–67.PubMedPubMedCentral
337.
Liu WCJ, Tamayo AT, Ruan C, Li L, Zhou S, Shen C, Young KH, Westin J, Davis RE, Hu S, Medeiros LJ, Ford RJ, Pham LV. Preclinical efficacy and biological effects of the oral proteasome inhibitor ixazomib in diffuse large B-cell lymphoma.pdf. Oncotarget. 2017;9:346.PubMedPubMedCentral
338.
Chitta K, Paulus A, Akhtar S, Blake MK, Caulfield TR, Novak AJ, Ansell SM, Advani P, Ailawadhi S, Sher T, et al. Targeted inhibition of the deubiquitinating enzymes, USP14 and UCHL5, induces proteotoxic stress and apoptosis in Waldenstrom macroglobulinaemia tumour cells. Br J Haematol. 2015;169(3):377–90.PubMedPubMedCentral
339.
Hientz K, Mohr A, Bhakta-Guha D, Efferth T. The role of p53 in cancer drug resistance and targeted chemotherapy. Oncotarget. 2017;8(5):8921–46.PubMed
340.
Luo Q, Pan W, Zhou S, Wang G, Yi H, Zhang L, Yan X, Yuan L, Liu Z, Wang J, et al. A novel BCL2 inhibitor APG-2575 exerts synthetic lethality with BTK or MDM2-p53 inhibitor in diffuse large B-cell lymphoma. Oncol Res. 2020;28(4):331–44.PubMedPubMedCentral
341.
Ceder S, Eriksson SE, Cheteh EH, Dawar S, Corrales Benitez M, Bykov VJN, Fujihara KM, Grandin M, Li X, Ramm S, et al. A thiol-bound drug reservoir enhances APR-246-induced mutant p53 tumor cell death. EMBO Mol Med. 2021;13(2):852.
342.
Harris SL, Levine AJ. The p53 pathway: positive and negative feedback loops. Oncogene. 2005;24(17):2899–908.PubMed
343.
Sallman DA, DeZern AE, Garcia-Manero G, Steensma DP, Roboz GJ, Sekeres MA, Cluzeau T, Sweet KL, McLemore A, McGraw KL, et al. Eprenetapopt (APR-246) and azacitidine in TP53-mutant myelodysplastic syndromes. J Clin Oncol Off J Am Soc Clin Oncol. 2021;39(14):1584–94.
344.
Ding Q, Zhang Z, Liu JJ, Jiang N, Zhang J, Ross TM, Chu XJ, Bartkovitz D, Podlaski F, Janson C, et al. Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development. J Med Chem. 2013;56(14):5979–83.PubMed
345.
Montesinos PBB, Catalani O, Esteve J, Gamel K, Konopleva MY, Martinelli G, Monnet A, Papayannidis C, Park A, Récher C, Rodríguez-Veiga R, Röllig C, Vey N, Wei AH, Yoon SS, Fenaux P. MIRROS_ a randomized, placebo-controlled, Phase III trial of cytarabine ± idasanutlin in relapsed or refractory acute myeloid leukemia. Fut Oncol. 2020;16:807–15.
346.
347.
Luo B, Huang L, Gu Y, Li C, Lu H, Chen G, Peng Z, Feng Z. Expression of exportin-1 in diffuse large B-cell lymphoma: immunohistochemistry and TCGA analyses. Int J Clin Exp Pathol. 2018;11(12):5547–60.PubMedPubMedCentral
348.
Deng M, Zhang M, Xu-Monette ZY, Pham LV, Tzankov A, Visco C, Fang X, Bhagat G, Zhu F, Dybkaer K, et al. XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53. J Hematol Oncol. 2020;13(1):148.PubMedPubMedCentral
349.
Liu Y, Azizian NG, Dou Y, Pham LV, Li Y. Simultaneous targeting of XPO1 and BCL2 as an effective treatment strategy for double-hit lymphoma. J Hematol Oncol. 2019;12(1):119.PubMedPubMedCentral
350.
Ben-Barouch S, Kuruvilla J. Selinexor (KTP-330) - a selective inhibitor of nuclear export (SINE): anti-tumor activity in diffuse large B-cell lymphoma (DLBCL). Expert Opin Investig Drugs. 2020;29(1):15–21.PubMed
351.
Toyokuni S. Mysterious link between iron overload and CDKN2A/2B. J Clin Biochem Nutr. 2011;48(1):46–9.PubMed
352.
Young RJ, Waldeck K, Martin C, Foo JH, Cameron DP, Kirby L, Do H, Mitchell C, Cullinane C, Liu W, et al. Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines. Pigment Cell Melanoma Res. 2014;27(4):590–600.PubMed
353.
Rhee K, Bresnahan W, Hirai A, Hirai M, Thompson EA. c-Myc and cyclin D3 (CcnD3) genes are independent targets for glucocorticoid inhibition of lymphoid cell proliferation. Cancer Res. 1995;55(18):4188–95.PubMed
354.
Cheng W, Yang Z, Wang S, Li Y, Wei H, Tian X, Kan Q. Recent development of CDK inhibitors: an overview of CDK/inhibitor co-crystal structures. Eur J Med Chem. 2019;164:615–39.PubMed
355.
Tanaka Y, Momose S, Tabayashi T, Sawada K, Yamashita T, Higashi M, Sagawa M, Tokuhira M, Rosenwald A, Kizaki M, et al. Abemaciclib, a CDK4/6 inhibitor, exerts preclinical activity against aggressive germinal center-derived B-cell lymphomas. Cancer Sci. 2020;111(2):749–59.PubMedPubMedCentral
356.
Lacrima K, Rinaldi A, Vignati S, Martin V, Tibiletti MG, Gaidano G, Catapano CV, Bertoni F. Cyclin-dependent kinase inhibitor seliciclib shows in vitro activity in diffuse large B-cell lymphomas. Leuk Lymphoma. 2007;48(1):158–67.PubMed
357.
Miljkovic MD, Roschewski M, Dunleavy K, Wilson WH. Hybrid dosing of the cyclin-dependent kinase (CDK) inhibitor flavopiridol in relapsed/refractory mantle cell lymphoma and diffuse large B-cell lymphoma. Leuk Lymphoma. 2019;60(13):3320–3.PubMedPubMedCentral
358.
Wei M, Zhao R, Cao Y, Wei Y, Li M, Dong Z, Liu Y, Ruan H, Li Y, Cao S, et al. First orally bioavailable prodrug of proteolysis targeting chimera (PROTAC) degrades cyclin-dependent kinases 2/4/6 in vivo. Eur J Med Chem. 2021;209:112.
359.
Jiang B, Gao Y, Che J, Lu W, Kaltheuner IH, Dries R, Kalocsay M, Berberich MJ, Jiang J, You I, et al. Discovery and resistance mechanism of a selective CDK12 degrader. Nat Chem Biol. 2021;17(6):675–83.PubMedPubMedCentral
360.
Falgas A, Pallares V, Unzueta U, Cespedes MV, Arroyo-Solera I, Moreno MJ, Sierra J, Gallardo A, Mangues MA, Vazquez E, et al. A CXCR4-targeted nanocarrier achieves highly selective tumor uptake in diffuse large B-cell lymphoma mouse models. Haematologica. 2020;105(3):741–53.PubMedPubMedCentral
361.
Falgas A, Pallares V, Serna N, Sanchez-Garcia L, Sierra J, Gallardo A, Alba-Castellon L, Alamo P, Unzueta U, Villaverde A, et al. Selective delivery of T22-PE24-H6 to CXCR4(+) diffuse large B-cell lymphoma cells leads to wide therapeutic index in a disseminated mouse model. Theranostics. 2020;10(12):5169–80.PubMedPubMedCentral
362.
Nayak L, Iwamoto FM, LaCasce A, Mukundan S, Roemer MGM, Chapuy B, Armand P, Rodig SJ, Shipp MA. PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma. Blood. 2017;129(23):3071–3.PubMedPubMedCentral
363.
Rutherford SC, Abramson JS, Bartlett NL, Barta SK, Khan N, Joyce R, Maddocks K, Ali-Shaw T, Senese S, Yuan Y, et al. Venetoclax with dose-adjusted EPOCH-R as initial therapy for patients with aggressive B-cell lymphoma: a single-arm, multicentre, phase 1 study. Lancet Haematol. 2021;8(11):e818–27.PubMed
364.
Davies A, Cummin TE, Barrans S, Maishman T, Mamot C, Novak U, Caddy J, Stanton L, Kazmi-Stokes S, McMillan A, et al. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20(5):649–62.PubMedPubMedCentral
365.
Oki Y, Kelly KR, Flinn I, Patel MR, Gharavi R, Ma A, Parker J, Hafeez A, Tuck D, Younes A. CUDC-907 in relapsed/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial. Haematologica. 2017;102(11):1923–30.PubMedPubMedCentral
366.
Ji J, Liu Z, Kuang P, Dong T, Chen X, Li J, Zhang C, Liu J, Zhang L, Shen K, et al. A new conditioning regimen with chidamide, cladribine, gemcitabine and busulfan significantly improve the outcome of high-risk or relapsed/refractory non-Hodgkin’s lymphomas. Int J Cancer. 2021;149(12):2075–82.PubMed
367.
Brem EA, Li H, Beaven AW, Caimi PF, Cerchietti L, Alizadeh AA, Olin R, Henry NL, Dillon H, Little RF, et al. SWOG 1918: A phase II/III randomized study of R-miniCHOP with or without oral azacitidine (CC-486) in participants age 75 years or older with newly diagnosed aggressive non-Hodgkin lymphomas—aiming to improve therapy, outcomes, and validate a prospective frailty tool. J Geriatr Oncol. 2022;13(2):258–64.PubMed
368.
Martin P, Bartlett NL, Chavez JC, Reagan JL, Smith SM, LaCasce AS, Jones J, Drew J, Wu C, Mulvey E, et al. Phase 1 study of oral azacitidine (CC-486) plus R-CHOP in previously untreated intermediate- to high-risk DLBCL. Blood. 2022;139(8):1147–59.PubMed
369.
Seymour EK, Khan HY, Li Y, Chaker M, Muqbil I, Aboukameel A, Ramchandren R, Houde C, Sterbis G, Yang J, et al. Selinexor in combination with R-CHOP for frontline treatment of non-hodgkin lymphoma: results of a phase I study. Clin Cancer Res Off J Am Assoc Cancer Res. 2021;27(12):3307–16.
370.
Schoch LK, Asiama A, Zahurak M, Shanbhag S, Hurtt J, Sawyer K, Swinnen LJ, Wagner-Johnston N, Jones RJ, Ambinder RF, et al. Pharmacokinetically-targeted dosed everolimus maintenance therapy in lymphoma patients. Cancer Chemother Pharmacol. 2018;81(2):347–54.PubMed
371.
Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010;463(7277):88–92.PubMedPubMedCentral
372.
Dubois S, Mareschal S, Cornic M, Picquenot J-M, Bertrand P, Bohers E, Maingonnat C, Viailly P-J, Ruminy P, Alcantara M, et al. Targeted EZH2 inhibitors in diffuse large B-cell lymphoma (DLBCL): immunohistochemical and mutational profiles of patients may determine candidates for treatment. Blood. 2014;124(21):1656–1656.
Metadata
Title
Altered pathways and targeted therapy in double hit lymphoma
Authors
Yuxin Zhuang
Jinxin Che
Meijuan Wu
Yu Guo
Yongjin Xu
Xiaowu Dong
Haiyan Yang
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2022
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-022-01249-9

Other articles of this Issue 1/2022

Journal of Hematology & Oncology 1/2022 Go to the issue

Review

Evidence-based expert consensus on the management of primary central nervous system lymphoma in China

Review

Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation

Review

Worked to the bone: antibody-based conditioning as the future of transplant biology

Correspondence

C3aR costimulation enhances the antitumor efficacy of CAR-T cell therapy through Th17 expansion and memory T cell induction

Research

Hypoxia-induced exosomal circPDK1 promotes pancreatic cancer glycolysis via c-myc activation by modulating miR-628-3p/BPTF axis and degrading BIN1

Research

Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2)
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits