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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2015

Open Access 01-12-2015 | Review

ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development

Authors: Shundong Cang, Chaitanya Iragavarapu, John Savooji, Yongping Song, Delong Liu

Published in: Journal of Hematology & Oncology | Issue 1/2015

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Abstract

With the advent of new agents targeting CD20, Bruton’s tyrosine kinase, and phosphoinositol-3 kinase for chronic lymphoid leukemia (CLL), more treatment options exist than ever before. B-cell lymphoma-2 (BCL-2) plays a major role in cellular apoptosis and is a druggable target. Small molecule inhibitors of BCL-2 are in active clinical studies. ABT-199 (venetoclax, RG7601, GDC-0199) has been granted breakthrough designation by FDA for relapsed or refractory CLL with 17p deletion. In this review, we summarized the latest clinical development of ABT-199/venetoclax and other novel agents targeting the BCL-2 proteins.
Literature
1.
2.
3.
4.
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.PubMedCentralCrossRefPubMed
5.
6.
7.
Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997–1007.PubMedCentralCrossRefPubMed
8.
Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101–10.CrossRefPubMed
9.
Mellor J, Brown M, Irving H, Zalcberg J, Dobrovic A. A critical review of the role of Fc gamma receptor polymorphisms in the response to monoclonal antibodies in cancer. J Hematol Oncol. 2013;6(1):1.PubMedCentralCrossRefPubMed
10.
11.
Wu J, Fu J, Zhang M, Liu D. AFM13: a first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy. J Hematol Oncol. 2015;8:96.PubMedCentralCrossRefPubMed
12.
Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363(19):1812–21.CrossRefPubMed
13.
Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, et al. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015;385(9980):1873–83.CrossRefPubMed
14.
Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–9.PubMedCentralCrossRefPubMed
15.
Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.CrossRefPubMed
16.
Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33(17):1974–82.CrossRefPubMed
17.
Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372(21):2006–17.CrossRefPubMed
18.
Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.CrossRefPubMed
19.
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.CrossRefPubMed
20.
Shi L, Chen S, Yang L, Li Y. The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies. J Hematol Oncol. 2013;6(1):74.PubMedCentralCrossRefPubMed
21.
22.
23.
Byrd JC, Brown JR, O’Brien S, Barrientos JC, Kay NE, Reddy NM, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213–23.PubMedCentralCrossRefPubMed
24.
Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32–42.PubMedCentralCrossRefPubMed
25.
Han E, Li X-l, Wang C-r, Li T-f, Han S-Y. Chimeric antigen receptor-engineered T cells for cancer immunotherapy: progress and challenges. J Hematol Oncol. 2013;6(1):47.PubMedCentralCrossRefPubMed
26.
Haso W, Lee DW, Shah NN, Stetler-Stevenson M, Yuan CM, Pastan IH, et al. Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood. 2012;121(7):1165–74.CrossRefPubMed
27.
Ruella M, Barrett D, Kenderian SS, Shestova O, Hofmann TJ, Scholler J, et al. Novel chimeric antigen receptor T cells for the treatment of CD19-negative relapses occurring after CD19-targeted immunotherapies. Blood. 2014;124(21):966.
28.
Chen Y, Liu D. Chimeric antigen receptor (CAR)-directed adoptive immunotherapy: a new era in targeted cancer therapy. Stem Cell Investig. 2014;1:2.
29.
30.
Reusch U, Burkhardt C, Fucek I, Le Gall F, Le Gall M, Hoffmann K, et al. A novel tetravalent bispecific TandAb (CD30/CD16A) efficiently recruits NK cells for the lysis of CD30+ tumor cells. MAbs. 2014;6(3):728–73.CrossRefPubMed
31.
Rothe A, Sasse S, Topp MS, Eichenauer DA, Hummel H, Reiners KS, et al. A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2015;125(26):4024–31.PubMedCentralCrossRefPubMed
32.
Breton C, Nahimana A, Aubry D, Macoin J, Moretti P, Bertschinger M, et al. A novel anti-CD19 monoclonal antibody (GBR 401) with high killing activity against B cell malignancies. J Hematol Oncol. 2014;7(1):33.PubMedCentralCrossRefPubMed
33.
Wu J, Fu J, Zhang M, Liu D. Blinatumomab: a bispecific T cell engager (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia. J Hematol Oncol. 2015;8:104.PubMedCentralCrossRefPubMed
34.
Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984;226(4678):1097–9.CrossRefPubMed
35.
36.
Tsujimoto Y. Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria? Genes Cells. 1998;3(11):697–707.CrossRefPubMed
37.
McClintock DS, Santore MT, Lee VY, Brunelle J, Budinger GR, Zong WX, et al. Bcl-2 family members and functional electron transport chain regulate oxygen deprivation-induced cell death. Mol Cell Biol. 2002;22(1):94–104.PubMedCentralCrossRefPubMed
38.
Yamaguchi H, Bhalla K, Wang HG. Bax plays a pivotal role in thapsigargin-induced apoptosis of human colon cancer HCT116 cells by controlling Smac/Diablo and Omi/HtrA2 release from mitochondria. Cancer Res. 2003;63(7):1483–9.PubMed
39.
Susin SA, Zamzami N, Castedo M, Hirsch T, Marchetti P, Macho A, et al. Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J Exp Med. 1996;184(4):1331–41.CrossRefPubMed
40.
Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 1997;275(5303):1132–6.CrossRefPubMed
41.
Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, et al. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997;275(5303):1129–32.CrossRefPubMed
42.
Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science. 1998;281(5381):1322–6.CrossRefPubMed
43.
Kelekar A, Thompson CB. Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol. 1998;8(8):324–30.CrossRefPubMed
44.
Chao DT, Korsmeyer SJ. BCL-2 family: regulators of cell death. Annu Rev Immunol. 1998;16:395–419.CrossRefPubMed
45.
Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435(7042):677–81.CrossRefPubMed
46.
Chauhan D, Velankar M, Brahmandam M, Hideshima T, Podar K, Richardson P, et al. A novel Bcl-2/Bcl-X(L)/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma. Oncogene. 2007;26(16):2374–80.CrossRefPubMed
47.
Kline MP, Rajkumar SV, Timm MM, Kimlinger TK, Haug JL, Lust JA, et al. ABT-737, an inhibitor of Bcl-2 family proteins, is a potent inducer of apoptosis in multiple myeloma cells. Leukemia. 2007;21(7):1549–60.CrossRefPubMed
48.
Konopleva M, Contractor R, Tsao T, Samudio I, Ruvolo PP, Kitada S, et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell. 2006;10(5):375–88.CrossRefPubMed
49.
Del Gaizo MV, Schlis KD, Sallan SE, Armstrong SA, Letai A. BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia. Blood. 2008;111(4):2300–9.CrossRef
50.
Ishitsuka K, Kunami N, Katsuya H, Nogami R, Ishikawa C, Yotsumoto F, et al. Targeting Bcl-2 family proteins in adult T-cell leukemia/lymphoma: in vitro and in vivo effects of the novel Bcl-2 family inhibitor ABT-737. Cancer Lett. 2012;317(2):218–25.CrossRefPubMed
51.
Mason KD, Vandenberg CJ, Scott CL, Wei AH, Cory S, Huang DC, et al. In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas. Proc Natl Acad Sci U S A. 2008;105(46):17961–6.PubMedCentralCrossRefPubMed
52.
High LM, Szymanska B, Wilczynska-Kalak U, Barber N, O’Brien R, Khaw SL, et al. The Bcl-2 homology domain 3 mimetic ABT-737 targets the apoptotic machinery in acute lymphoblastic leukemia resulting in synergistic in vitro and in vivo interactions with established drugs. Mol Pharmacol. 2010;77(3):483–94.CrossRefPubMed
53.
Kang MH, Kang YH, Szymanska B, Wilczynska-Kalak U, Sheard MA, Harned TM, et al. Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo. Blood. 2007;110(6):2057–66.CrossRefPubMed
54.
Lock R, Carol H, Houghton PJ, Morton CL, Kolb EA, Gorlick R, et al. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;50(6):1181–9.CrossRefPubMed
55.
Ackler S, Xiao Y, Mitten MJ, Foster K, Oleksijew A, Refici M, et al. ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. Mol Cancer Ther. 2008;7(10):3265–74.CrossRefPubMed
56.
Suryani S, Carol H, Chonghaile TN, Frismantas V, Sarmah C, High L, et al. Cell and molecular determinants of in vivo efficacy of the BH3 mimetic ABT-263 against pediatric acute lymphoblastic leukemia xenografts. Clin Cancer Res. 2014;20(17):4520–31.PubMedCentralCrossRefPubMed
57.
Ackler S, Mitten MJ, Chen J, Clarin J, Foster K, Jin S, et al. Navitoclax (ABT-263) and bendamustine +/- rituximab induce enhanced killing of non-Hodgkin’s lymphoma tumours in vivo. Br J Pharmacol. 2012;167(4):881–91.PubMedCentralCrossRefPubMed
58.
Ackler S, Mitten MJ, Foster K, Oleksijew A, Refici M, Tahir SK, et al. The Bcl-2 inhibitor ABT-263 enhances the response of multiple chemotherapeutic regimens in hematologic tumors in vivo. Cancer Chemother Pharmacol. 2010;66(5):869–80.CrossRefPubMed
59.
Wilson WH, O’Connor OA, Czuczman MS, LaCasce AS, Gerecitano JF, Leonard JP, et al. Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol. 2010;11(12):1149–59.PubMedCentralCrossRefPubMed
60.
Roberts AW, Seymour JF, Brown JR, Wierda WG, Kipps TJ, Khaw SL, et al. Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol. 2012;30(5):488–96.CrossRefPubMed
61.
Zhang H, Nimmer PM, Tahir SK, Chen J, Fryer RM, Hahn KR, et al. Bcl-2 family proteins are essential for platelet survival. Cell Death Differ. 2007;14(5):943–51.PubMed
62.
Mason KD, Carpinelli MR, Fletcher JI, Collinge JE, Hilton AA, Ellis S, et al. Programmed anuclear cell death delimits platelet life span. Cell. 2007;128(6):1173–86.CrossRefPubMed
63.
Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19(2):202–8.CrossRefPubMed
64.
Vogler M, Dinsdale D, Dyer MJ, Cohen GM. ABT-199 selectively inhibits BCL2 but not BCL2L1 and efficiently induces apoptosis of chronic lymphocytic leukaemic cells but not platelets. Br J Haematol. 2013;163(1):139–42.CrossRefPubMed
65.
Pan R, Hogdal LJ, Benito JM, Bucci D, Han L, Borthakur G, et al. Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia. Cancer Discov. 2014;4(3):362–75.PubMedCentralCrossRefPubMed
66.
Khaw SL, Merino D, Anderson MA, Glaser SP, Bouillet P, Roberts AW, et al. Both leukaemic and normal peripheral B lymphoid cells are highly sensitive to the selective pharmacological inhibition of prosurvival Bcl-2 with ABT-199. Leukemia. 2014;28(6):1207–15.CrossRefPubMed
67.
Vandenberg CJ, Cory S. ABT-199, a new Bcl-2-specific BH3 mimetic, has in vivo efficacy against aggressive Myc-driven mouse lymphomas without provoking thrombocytopenia. Blood. 2013;121(12):2285–8.PubMedCentralCrossRefPubMed
68.
Peirs S, Matthijssens F, Goossens S, Van de Walle I, Ruggero K, de Bock CE, et al. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014;124(25):3738–47.CrossRefPubMed
69.
Bodo J, Zhao X, Smith MR, Hsi ED. Activity of ABT-199 and acquired resistance in follicular lymphoma cells. Blood. 2014;124(21):3635–5.
70.
Carter BZ, Mak PY, Mu H, Zhou H, Mak DH, Schober WD, et al. Cooperative targeting of Bcl-2 family proteins by ABT-199 (GDC-0199) and tyrosine kinase inhibitors to eradicate blast crisis CML and CML stem/progenitor cells. Blood. 2014;124(21):512–2.
71.
Portell CA, Axelrod M, Brett LK, Gordon VL, Capaldo B, Xing JC, et al. Synergistic cytotoxicity of ibrutinib and the BCL2 antagonist, ABT-199(GDC-0199) in mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL): molecular analysis reveals mechanisms of target interactions. Blood. 2014;124(21):509–9.
72.
Gerecitano J. SINE (selective inhibitor of nuclear export) - translational science in a new class of anti-cancer agents. J Hematol Oncol. 2014;7(1):67.PubMedCentralCrossRefPubMed
73.
Gravina G, Senapedis W, McCauley D, Baloglu E, Shacham S, Festuccia C. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol. 2014;7(1):85.PubMedCentralCrossRefPubMed
74.
Gravina G, Tortoreto M, Mancini A, Addis A, Di Cesare E, Lenzi A, et al. XPO1/CRM1-selective inhibitors of nuclear export (SINE) reduce tumor spreading and improve overall survival in preclinical models of prostate cancer (PCa). J Hematol Oncol. 2014;7(1):46.PubMedCentralCrossRefPubMed
75.
76.
77.
Tabe Y, Harada M, Miyamae Y, Kazuno S, Fujimura T, Ueno T, et al. Selective inhibitor of nuclear export selinexor (KPT-330) and BCL2 inhibitor ABT-199 enhance the anti-lymphoma effect of BTK inhibitor ibrutinib in mantle cell lymphoma. Blood. 2014;124(21):2254–4.
78.
79.
Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW. MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proc Natl Acad Sci U S A. 1993;90(8):3516–20.PubMedCentralCrossRefPubMed
80.
Klanova M, Andera L, Soukup J, Jan B, Svadlenka J, Benesova S, et al. MCL1 targeting agent homoharringtonine exerts strong cytotoxicity towards diffuse large B-cell lymphoma (DLBCL) cells and synergizes with BCL2 targeting agent ABT199 in eliminating BCL2-positive DLBCL cells. Blood. 2014;124(21):3645–5.
81.
Davids MS, Pagel JM, Kahl BS, Wierda WG, Miller TP, Gerecitano JF, et al. Bcl-2 inhibitor ABT-199 (GDC-0199) monotherapy shows anti-tumor activity including complete remissions in high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Blood. 2013;122(21):872–2.
82.
83.
Seymour JF, Davids MS, Pagel JM, Kahl BS, Wierda WG, Puvvada S, et al. ABT-199 (GDC-0199) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): high complete- response rate and durable disease control. ASCO Meeting Abstr. 2014;32(15_suppl):7015.
84.
Davids MS, Seymour JF, Gerecitano JF, Kahl BS, Pagel JM, Wierda WG, et al. Phase I study of ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL): responses observed in diffuse large B-cell (DLBCL) and follicular lymphoma (FL) at higher cohort doses. ASCO Meeting Abstr. 2014;32(15_suppl):8522.
85.
Konopleva M, Pollyea DA, Potluri J, Chyla BJ, Busman T, McKeegan E, et al. A phase 2 study of ABT-199 (GDC-0199) in patients with acute myelogenous leukemia (AML). Blood. 2014;124(21):118–8.
86.
Ma S, Seymour JF, Lanasa MC, Kipps TJ, Barrientos JC, Davids MS, et al. ABT-199 (GDC-0199) combined with rituximab (R) in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Interim results of a phase 1b study. ASCO Meeting Abstr. 2014;32(15_suppl):7013.
87.
Roberts AW, Ma S, Brander DM, Kipps TJ, Barrientos JC, Davids MS, et al. Determination of recommended phase 2 dose of ABT-199 (GDC-0199) combined with rituximab (R) in patients with relapsed / refractory (R/R) chronic lymphocytic leukemia (CLL). Blood. 2014;124(21):325–5.
88.
Mobasher M, Huang J, Elstrom RL, Elhamy M, Bernaards C, Hallek MJ, et al. Multicenter, phase III, open-label, randomized study in relapsed/refractory CLL to evaluate the benefit of GDC-0199 (ABT-199) plus rituximab compared with bendamustine plus rituximab. ASCO Meeting Abstr. 2014;32(15_suppl):TPS7120.
89.
de Vos S, Flowers CR, Wang D, Swinnen LJ, Fowler N, Reid E, et al. The BCL-2 inhibitor ABT-199 (GDC-0199) in combination with bendamustine and rituximab in patients with relapsed or refractory non-Hodgkin’s lymphoma. Blood. 2014;124(21):1722.
90.
Salles GA, Boyd TE, Morschhauser F, Wendtner C-M, Lymp J, Hilger J, et al. Preliminary results of a phase 1b study (GO28440) combining GDC-0199 (ABT-199) with bendamustine/rituximab in patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia. Blood. 2014;124(21):3337.
91.
Flinn I, Brunvand M, Dyer MJ, Hillman P, Jones J, Lymp J, et al. Preliminary results of a phase 1b study (GP28331) combining GDC-0199 (ABT-199) and obinutuzumab in patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia. Blood. 2014;124(21):4687.
92.
Wierda WG, Seymour JF, Roberts AW, Puvvada S, Davids MS, Wong S, et al. A phase 2 open-label study of the efficacy of ABT-199 (GDC-0199) in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) harboring 17p deletion. ASCO Meeting Abstr. 2014;32(15_suppl):TPS7121.
93.
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.CrossRefPubMed
94.
Choudhary GS, Al-Harbi S, Mazumder S, Hill BT, Smith MR, Bodo J, et al. MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies. Cell Death Dis. 2015;6:e1593.CrossRefPubMed
95.
Thijssen R, Slinger E, Weller K, Geest CR, Beaumont T, van Oers MH, et al. Resistance to ABT-199 induced by microenvironmental signals in chronic lymphocytic leukemia can be counteracted by CD20 antibodies or kinase inhibitors. Haematologica. 2015;100(8):e302–6.PubMed
Metadata
Title
ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development
Authors
Shundong Cang
Chaitanya Iragavarapu
John Savooji
Yongping Song
Delong Liu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-015-0224-3

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