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

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cellular Oncology
Published in: Cellular Oncology 2/2019

01-04-2019 | Review

Therapeutic targeting potential of chromatin-associated proteins in MLL-rearranged acute leukemia

Authors: Xin Xu, Björn Schneider

Published in: Cellular Oncology | Issue 2/2019

Login to get access

Abstract

Background

Acute leukemias (AL) with a Mixed Lineage Leukemia (MLL) gene rearrangement (MLLr) represent a group of leukemic entities conferring intermediate to adverse prognoses. Multiple chromatin-associated proteins have been shown to play essential roles during the genesis of MLLr AL. Some chromatin-associated proteins function as negative regulators of MLLr AL whereas others are required for leukemic initiation or maintenance - the latter group constituting potential therapeutic targets. Most of the identified proteins have been functionally analyzed using experimental models with human/murine normal cells transformed by MLL-AF9 or other MLL fusion products, which may recapitulate most but not all aspects of human AML, such as immune system interactions – features of which the importance is rapidly emerging.

Conclusions

Here, we review chromatin-associated proteins fundamental to MLLr AL development, highlighting those with targeting potential by small molecule inhibitors. In particular, we focus on synthetic targeting of multiple chromatin-associated proteins, a strategy that shows superior therapeutic efficacy and offers hope for overcoming drug resistance.
Literature
1.
C. Röllig, M. Bornhäuser, C. Thiede, F. Taube, M. Kramer, B. Mohr, W. Aulitzky, H. Bodenstein, H.-J. Tischler, R. Stuhlmann, U. Schuler, F. Stölzel, M. von Bonin, H. Wandt, K. Schäfer-Eckart, M. Schaich, G. Ehninger, Long-term prognosis of acute myeloid leukemia according to the new genetic risk classification of the European LeukemiaNet recommendations: evaluation of the proposed reporting system. J. Clin. Oncol. 29, 2758–2765 (2011)CrossRefPubMed
2.
C.H. Pui, F.G. Behm, J.R. Downing, M.L. Hancock, S.A. Shurtleff, R.C. Ribeiro, D.R. Head, H.H. Mahmoud, J.T. Sandlund, W.L. Furman, 11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia. J. Clin. Oncol. 12, 909–915 (1994)CrossRefPubMed
3.
C. Meyer, T. Burmeister, D. Gröger, G. Tsaur, L. Fechina, A. Renneville, R. Sutton, N.C. Venn, M. Emerenciano, M.S. Pombo-de-Oliveira, C. Barbieri Blunck, B. Almeida Lopes, J. Zuna, J. Trka, P. Ballerini, H. Lapillonne, M. de Braekeleer, G. Cazzaniga, L. Corral Abascal, V.H.J. van der Velden, E. Delabesse, T.S. Park, S.H. Oh, M.L.M. Silva, T. Lund-Aho, V. Juvonen, A.S. Moore, O. Heidenreich, J. Vormoor, E. Zerkalenkova, Y. Olshanskaya, C. Bueno, P. Menendez, A. Teigler-Schlegel, U. Zur Stadt, J. Lentes, G. Göhring, A. Kustanovich, O. Aleinikova, B.W. Schäfer, S. Kubetzko, H.O. Madsen, B. Gruhn, X. Duarte, P. Gameiro, E. Lippert, A. Bidet, J.M. Cayuela, E. Clappier, C.N. Alonso, C.M. Zwaan, M.M. van den Heuvel-Eibrink, S. Izraeli, L. Trakhtenbrot, P. Archer, J. Hancock, A. Möricke, J. Alten, M. Schrappe, M. Stanulla, S. Strehl, A. Attarbaschi, M. Dworzak, O.A. Haas, R. Panzer-Grümayer, L. Sedék, T. Szczepański, A. Caye, L. Suarez, H. Cavé, R. Marschalek, The MLL recombinome of acute leukemias in 2017. Leukemia 32, 273–284 (2018)CrossRefPubMed
4.
A.V. Krivtsov, S.A. Armstrong, MLL translocations, histone modifications and leukaemia stem-cell development. Nat. Rev. Cancer 7, 823–833 (2007)CrossRefPubMed
5.
6.
Y. Wang, A.V. Krivtsov, A.U. Sinha, T.E. North, W. Goessling, Z. Feng, L.I. Zon, S.A. Armstrong, The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science 327, 1650–1653 (2010)CrossRefPubMedPubMedCentral
7.
L. Zhu, Q. Li, S.H.K. Wong, M. Huang, B.J. Klein, J. Shen, L. Ikenouye, M. Onishi, D. Schneidawind, C. Buechele, L. Hansen, J. Duque-Afonso, F. Zhu, G.M. Martin, O. Gozani, R. Majeti, T.G. Kutateladze, M.L. Cleary, ASH1L links histone H3 lysine 36 dimethylation to MLL leukemia. Cancer Discov. 6, 770–783 (2016)CrossRefPubMedPubMedCentral
8.
Y. Zheng, H. Zhang, Y. Wang, X. Li, P. Lu, F. Dong, Y. Pang, S. Ma, H. Cheng, S. Hao, F. Tang, W. Yuan, X. Zhang, T. Cheng, Loss of Dnmt3b accelerates MLL-AF9 leukemia progression. Leukemia 30, 2373–2384 (2016)CrossRefPubMed
9.
M.-J. Chang, H. Wu, N.J. Achille, M.R. Reisenauer, C.-W. Chou, N.J. Zeleznik-Le, C.S. Hemenway, W. Zhang, Histone H3 lysine 79 methyltransferase Dot1 is required for immortalization by MLL oncogenes. Cancer Res. 70, 10234–10242 (2010)CrossRefPubMedPubMedCentral
10.
K.M. Bernt, N. Zhu, A.U. Sinha, S. Vempati, J. Faber, A.V. Krivtsov, Z. Feng, N. Punt, A. Daigle, L. Bullinger, R.M. Pollock, V.M. Richon, A.L. Kung, S.A. Armstrong, MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell 20, 66–78 (2011)CrossRefPubMedPubMedCentral
11.
D.G. Valerio, H. Xu, M.E. Eisold, C.M. Woolthuis, T.K. Pandita, S.A. Armstrong, Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice. Blood 129, 48–59 (2017)CrossRefPubMedPubMedCentral
12.
T. Neff, A.U. Sinha, M.J. Kluk, N. Zhu, M.H. Khattab, L. Stein, H. Xie, S.H. Orkin, S.A. Armstrong, Polycomb repressive complex 2 is required for MLL-AF9 leukemia. Proc. Natl. Acad. Sci. U. S. A. 109, 5028–5033 (2012)CrossRefPubMedPubMedCentral
13.
B. Zhou, J. Wang, S.Y. Lee, J. Xiong, N. Bhanu, Q. Guo, P. Ma, Y. Sun, R.C. Rao, B.A. Garcia, J.L. Hess, Y. Dou, PRDM16 Suppresses MLL1r Leukemia via Intrinsic Histone Methyltransferase Activity. Mol. Cell 62, 222–236 (2016)CrossRefPubMedPubMedCentral
14.
N. Cheung, T.K. Fung, B.B. Zeisig, K. Holmes, J.K. Rane, K.A. Mowen, M.G. Finn, B. Lenhard, L.C. Chan, C.W.E. So, Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia. Cancer Cell 29, 32–48 (2016)CrossRefPubMedPubMedCentral
15.
S. Kaushik, F. Liu, K.J. Veazey, G. Gao, P. Das, L.F. Neves, K. Lin, Y. Zhong, Y. Lu, V. Giuliani, M.T. Bedford, S.D. Nimer, M.A. Santos, Genetic deletion or small-molecule inhibition of the arginine methyltransferase PRMT5 exhibit anti-tumoral activity in mouse models of MLL-rearranged AML. Leukemia 32, 499–509 (2018)CrossRefPubMed
16.
W.J. Harris, X. Huang, J.T. Lynch, G.J. Spencer, J.R. Hitchin, Y. Li, F. Ciceri, J.G. Blaser, B.F. Greystoke, A.M. Jordan, C.J. Miller, D.J. Ogilvie, T.C.P. Somervaille, The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell 21, 473–487 (2012)CrossRefPubMed
17.
N. Zhu, M. Chen, R. Eng, J. DeJong, A.U. Sinha, N.F. Rahnamay, R. Koche, F. Al-Shahrour, J.C. Minehart, C.-W. Chen, A.J. Deshpande, H. Xu, S.H. Chu, B.L. Ebert, R.G. Roeder, S.A. Armstrong, MLL-AF9- and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C. J. Clin. Invest. 126, 997–1011 (2016)CrossRefPubMedPubMedCentral
18.
P. Sroczynska, V.A. Cruickshank, J.-P. Bukowski, S. Miyagi, F.O. Bagger, J. Walfridsson, M.B. Schuster, B. Porse, K. Helin, shRNA screening identifies JMJD1C as being required for leukemia maintenance. Blood 123, 1870–1882 (2014)CrossRefPubMed
19.
S.H.K. Wong, D.L. Goode, M. Iwasaki, M.C. Wei, H.-P. Kuo, L. Zhu, D. Schneidawind, J. Duque-Afonso, Z. Weng, M.L. Cleary, The H3K4-Methyl epigenome regulates leukemia stem cell oncogenic potential. Cancer Cell 28, 198–209 (2015)CrossRefPubMedPubMedCentral
20.
H. Huang, X. Jiang, Z. Li, Y. Li, C.-X. Song, C. He, M. Sun, P. Chen, S. Gurbuxani, J. Wang, G.-M. Hong, A.G. Elkahloun, S. Arnovitz, J. Wang, K. Szulwach, L. Lin, C. Street, M. Wunderlich, M. Dawlaty, M.B. Neilly, R. Jaenisch, F.-C. Yang, J.C. Mulloy, P. Jin, P.P. Liu, J.D. Rowley, M. Xu, C. He, J. Chen, TET1 plays an essential oncogenic role in MLL-rearranged leukemia. Proc. Natl. Acad. Sci. U. S. A. 110, 11994–11999 (2013)CrossRefPubMedPubMedCentral
21.
J. Zuber, J. Shi, E. Wang, A.R. Rappaport, H. Herrmann, E.A. Sison, D. Magoon, J. Qi, K. Blatt, M. Wunderlich, M.J. Taylor, C. Johns, A. Chicas, J.C. Mulloy, S.C. Kogan, P. Brown, P. Valent, J.E. Bradner, S.W. Lowe, C.R. Vakoc, RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478, 524–528 (2011)CrossRefPubMedPubMedCentral
22.
C.Y. Fong, O. Gilan, E.Y.N. Lam, A.F. Rubin, S. Ftouni, D. Tyler, K. Stanley, D. Sinha, P. Yeh, J. Morison, G. Giotopoulos, D. Lugo, P. Jeffrey, S.C.-W. Lee, C. Carpenter, R. Gregory, R.G. Ramsay, S.W. Lane, O. Abdel-Wahab, T. Kouzarides, R.W. Johnstone, S.-J. Dawson, B.J.P. Huntly, R.K. Prinjha, A.T. Papenfuss, M.A. Dawson, BET inhibitor resistance emerges from leukaemia stem cells. Nature 525, 538–542 (2015)CrossRefPubMedPubMedCentral
23.
J. Tan, M. Jones, H. Koseki, M. Nakayama, A.G. Muntean, I. Maillard, J.L. Hess, CBX8, a polycomb group protein, is essential for MLL-AF9-induced leukemogenesis. Cancer Cell 20, 563–575 (2011)CrossRefPubMedPubMedCentral
24.
25.
A. Yokoyama, T.C.P. Somervaille, K.S. Smith, O. Rozenblatt-Rosen, M. Meyerson, M.L. Cleary, The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. Cell 123, 207–218 (2005)CrossRefPubMed
26.
E. Wang, S. Kawaoka, M. Yu, J. Shi, T. Ni, W. Yang, J. Zhu, R.G. Roeder, C.R. Vakoc, Histone H2B ubiquitin ligase RNF20 is required for MLL-rearranged leukemia. Proc. Natl. Acad. Sci. U. S. A. 110, 3901–3906 (2013)CrossRefPubMedPubMedCentral
27.
N. Rapin, B.T. Porse, Oncogenic fusion proteins expressed in immature hematopoietic cells fail to recapitulate the transcriptional changes observed in human AML. Oncogenesis 3, e106 (2014)CrossRefPubMedPubMedCentral
28.
G.D. Gregory, C.R. Vakoc, T. Rozovskaia, X. Zheng, S. Patel, T. Nakamura, E. Canaani, G.A. Blobel, Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes. Mol. Cell. Biol. 27, 8466–8479 (2007)CrossRefPubMedPubMedCentral
29.
Y. Tanaka, Z.-I. Katagiri, K. Kawahashi, D. Kioussis, S. Kitajima, Trithorax-group protein ASH1 methylates histone H3 lysine 36. Gene 397, 161–168 (2007)CrossRefPubMed
30.
H. Miyazaki, K. Higashimoto, Y. Yada, T.A. Endo, J. Sharif, T. Komori, M. Matsuda, Y. Koseki, M. Nakayama, H. Soejima, H. Handa, H. Koseki, S. Hirose, K. Nishioka, Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing. PLoS Genet. 9, e1003897 (2013)CrossRefPubMedPubMedCentral
31.
S. An, K.J. Yeo, Y.H. Jeon, J.-J. Song, Crystal structure of the human histone methyltransferase ASH1L catalytic domain and its implications for the regulatory mechanism. J. Biol. Chem. 286, 8369–8374 (2011)CrossRefPubMedPubMedCentral
32.
M. Jones, J. Chase, M. Brinkmeier, J. Xu, D.N. Weinberg, J. Schira, A. Friedman, S. Malek, J. Grembecka, T. Cierpicki, Y. Dou, S.A. Camper, I. Maillard, Ash1l controls quiescence and self-renewal potential in hematopoietic stem cells. J. Clin. Invest. 125, 2007–2020 (2015)CrossRefPubMedPubMedCentral
33.
M. Okano, D.W. Bell, D.A. Haber, E. Li, DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247–257 (1999)CrossRefPubMed
34.
S.-i. Mizuno, Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia. Blood 97, 1172–1179 (2001)CrossRefPubMed
35.
D. Watanabe, I. Suetake, S. Tajima, K. Hanaoka, Expression of Dnmt3b in mouse hematopoietic progenitor cells and spermatogonia at specific stages. Gene Expr. Patterns 5, 43–49 (2004)CrossRefPubMed
36.
T.J. Ley, L. Ding, M.J. Walter, M.D. McLellan, T. Lamprecht, D.E. Larson, C. Kandoth, J.E. Payton, J. Baty, J. Welch, C.C. Harris, C.F. Lichti, R.R. Townsend, R.S. Fulton, D.J. Dooling, D.C. Koboldt, H. Schmidt, Q. Zhang, J.R. Osborne, L. Lin, M. O'Laughlin, J.F. McMichael, K.D. Delehaunty, S.D. McGrath, L.A. Fulton, V.J. Magrini, T.L. Vickery, J. Hundal, L.L. Cook, J.J. Conyers, G.W. Swift, J.P. Reed, P.A. Alldredge, T. Wylie, J. Walker, J. Kalicki, M.A. Watson, S. Heath, W.D. Shannon, N. Varghese, R. Nagarajan, P. Westervelt, M.H. Tomasson, D.C. Link, T.A. Graubert, J.F. DiPersio, E.R. Mardis, R.K. Wilson, DNMT3A mutations in acute myeloid leukemia. N. Engl. J. Med. 363, 2424–2433 (2010)CrossRefPubMedPubMedCentral
37.
X.-J. Yan, J. Xu, Z.-H. Gu, C.-M. Pan, G. Lu, Y. Shen, J.-Y. Shi, Y.-M. Zhu, L. Tang, X.-W. Zhang, W.-X. Liang, J.-Q. Mi, H.-D. Song, K.-Q. Li, Z. Chen, S.-J. Chen, Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat. Genet. 43, 309–315 (2011)CrossRefPubMed
38.
M.J. Walter, L. Ding, D. Shen, J. Shao, M. Grillot, M. McLellan, R. Fulton, H. Schmidt, J. Kalicki-Veizer, M. O'Laughlin, C. Kandoth, J. Baty, P. Westervelt, J.F. DiPersio, E.R. Mardis, R.K. Wilson, T.J. Ley, T.A. Graubert, Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia 25, 1153–1158 (2011)CrossRefPubMedPubMedCentral
39.
L. Couronné, C. Bastard, O.A. Bernard, TET2 and DNMT3A mutations in human T-cell lymphoma. N. Engl. J. Med. 366, 95–96 (2012)CrossRefPubMed
40.
S. Hayette, X. Thomas, L. Jallades, K. Chabane, C. Charlot, I. Tigaud, S. Gazzo, S. Morisset, P. Cornillet-Lefebvre, A. Plesa, S. Huet, A. Renneville, G. Salles, F.E. Nicolini, J.-P. Magaud, M. Michallet, High DNA methyltransferase DNMT3B levels: a poor prognostic marker in acute myeloid leukemia. PLoS ONE 7, e51527 (2012)CrossRefPubMedPubMedCentral
41.
C. Niederwieser, J. Kohlschmidt, S. Volinia, S.P. Whitman, K.H. Metzeler, A.-K. Eisfeld, K. Maharry, P. Yan, D. Frankhouser, H. Becker, S. Schwind, A.J. Carroll, D. Nicolet, J.H. Mendler, J.P. Curfman, Y.-Z. Wu, M.R. Baer, B.L. Powell, J.E. Kolitz, J.O. Moore, T.H. Carter, R. Bundschuh, R.A. Larson, R.M. Stone, K. Mrózek, G. Marcucci, C.D. Bloomfield, Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia. Leukemia 29, 567–575 (2015)CrossRefPubMed
42.
I. Schulze, C. Rohde, M. Scheller-Wendorff, N. Bäumer, A. Krause, F. Herbst, P. Riemke, K. Hebestreit, P. Tschanter, Q. Lin, H. Linhart, L.A. Godley, H. Glimm, M. Dugas, W. Wagner, W.E. Berdel, F. Rosenbauer, C. Müller-Tidow, Increased DNA methylation of Dnmt3b targets impairs leukemogenesis. Blood 127, 1575–1586 (2016)CrossRefPubMed
43.
Q. Feng, H. Wang, H.H. Ng, H. Erdjument-Bromage, P. Tempst, K. Struhl, Y. Zhang, Methylation of H3-Lysine 79 Is Mediated by a New Family of HMTases without a SET Domain. Curr. Biol. 12, 1052–1058 (2002)CrossRefPubMed
44.
S.Y. Jo, E.M. Granowicz, I. Maillard, D. Thomas, J.L. Hess, Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation. Blood 117, 4759–4768 (2011)CrossRefPubMedPubMedCentral
45.
46.
A.T. Nguyen, O. Taranova, J. He, Y. Zhang, DOT1L, the H3K79 methyltransferase, is required for MLL-AF9-mediated leukemogenesis. Blood 117, 6912–6922 (2011)CrossRefPubMedPubMedCentral
47.
Y. Okada, Q. Feng, Y. Lin, Q. Jiang, Y. Li, V.M. Coffield, L. Su, G. Xu, Y. Zhang, hDOT1L links histone methylation to leukemogenesis. Cell 121, 167–178 (2005)CrossRefPubMed
48.
D. Mueller, C. Bach, D. Zeisig, M.-P. Garcia-Cuellar, S. Monroe, A. Sreekumar, R. Zhou, A. Nesvizhskii, A. Chinnaiyan, J.L. Hess, R.K. Slany, A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood 110, 4445–4454 (2007)CrossRefPubMedPubMedCentral
49.
E. Bitoun, P.L. Oliver, K.E. Davies, The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling. Hum. Mol. Genet. 16, 92–106 (2007)CrossRefPubMed
50.
S.C. Monroe, S.Y. Jo, D.S. Sanders, V. Basrur, K.S. Elenitoba-Johnson, R.K. Slany, J.L. Hess, MLL-AF9 and MLL-ENL alter the dynamic association of transcriptional regulators with genes critical for leukemia. Exp. Hematol. 39, 77–86.e1-5 (2011)CrossRefPubMed
51.
M. Mohan, H.-M. Herz, Y.-H. Takahashi, C. Lin, K.C. Lai, Y. Zhang, M.P. Washburn, L. Florens, A. Shilatifard, Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom). Genes Dev. 24, 574–589 (2010)CrossRefPubMedPubMedCentral
52.
A. Benedikt, S. Baltruschat, B. Scholz, A. Bursen, T.N. Arrey, B. Meyer, L. Varagnolo, A.M. Müller, M. Karas, T. Dingermann, R. Marschalek, The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures. Leukemia 25, 135–144 (2011)CrossRefPubMed
53.
S.R. Daigle, E.J. Olhava, C.A. Therkelsen, C.R. Majer, C.J. Sneeringer, J. Song, L.D. Johnston, M.P. Scott, J.J. Smith, Y. Xiao, L. Jin, K.W. Kuntz, R. Chesworth, M.P. Moyer, K.M. Bernt, J.-C. Tseng, A.L. Kung, S.A. Armstrong, R.A. Copeland, V.M. Richon, R.M. Pollock, Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 20, 53–65 (2011)CrossRefPubMedPubMedCentral
54.
S.R. Daigle, E.J. Olhava, C.A. Therkelsen, A. Basavapathruni, L. Jin, P.A. Boriack-Sjodin, C.J. Allain, C.R. Klaus, A. Raimondi, M.P. Scott, N.J. Waters, R. Chesworth, M.P. Moyer, R.A. Copeland, V.M. Richon, R.M. Pollock, Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood 122, 1017–1025 (2013)CrossRefPubMedPubMedCentral
55.
A.J. Deshpande, L. Chen, M. Fazio, A.U. Sinha, K.M. Bernt, D. Banka, S. Dias, J. Chang, E.J. Olhava, S.R. Daigle, V.M. Richon, R.M. Pollock, S.A. Armstrong, Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l. Blood 121, 2533–2541 (2013)CrossRefPubMedPubMedCentral
56.
S.M. Sarkaria, M.J. Christopher, J.M. Klco, T.J. Ley, Primary acute myeloid leukemia cells with IDH1 or IDH2 mutations respond to a DOT1L inhibitor in vitro. Leukemia 28, 2403–2406 (2014)CrossRefPubMedPubMedCentral
57.
M.W.M. Kühn, M.J. Hadler, S.R. Daigle, R.P. Koche, A.V. Krivtsov, E.J. Olhava, M.A. Caligiuri, G. Huang, J.E. Bradner, R.M. Pollock, S.A. Armstrong, MLL partial tandem duplication leukemia cells are sensitive to small molecule DOT1L inhibition. Haematologica 100, e190–e193 (2015)CrossRefPubMedPubMedCentral
58.
A.J. Deshpande, A. Deshpande, A.U. Sinha, L. Chen, J. Chang, A. Cihan, M. Fazio, C.-W. Chen, N. Zhu, R. Koche, L. Dzhekieva, G. Ibáñez, S. Dias, D. Banka, A. Krivtsov, M. Luo, R.G. Roeder, J.E. Bradner, K.M. Bernt, S.A. Armstrong, AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes. Cancer Cell 26, 896–908 (2014)CrossRefPubMedPubMedCentral
59.
R.E. Rau, B.A. Rodriguez, M. Luo, M. Jeong, A. Rosen, J.H. Rogers, C.T. Campbell, S.R. Daigle, L. Deng, Y. Song, S. Sweet, T. Chevassut, M. Andreeff, S.M. Kornblau, W. Li, M.A. Goodell, DOT1L as a therapeutic target for the treatment of DNMT3A-mutant acute myeloid leukemia. Blood 128, 971–981 (2016)CrossRefPubMedPubMedCentral
60.
C.T. Campbell, J.N. Haladyna, D.A. Drubin, T.M. Thomson, M.J. Maria, T. Yamauchi, N.J. Waters, E.J. Olhava, R.M. Pollock, J.J. Smith, R.A. Copeland, S.J. Blakemore, K.M. Bernt, S.R. Daigle, Mechanisms of Pinometostat (EPZ-5676) Treatment-Emergent Resistance in MLL-Rearranged Leukemia. Mol. Cancer Ther. 16, 1669–1679 (2017)CrossRefPubMed
61.
62.
C.R. Klaus, D. Iwanowicz, D. Johnston, C.A. Campbell, J.J. Smith, M.P. Moyer, R.A. Copeland, E.J. Olhava, M.P. Scott, R.M. Pollock, S.R. Daigle, A. Raimondi, DOT1L inhibitor EPZ-5676 displays synergistic antiproliferative activity in combination with standard of care drugs and hypomethylating agents in MLL-rearranged leukemia cells. J. Pharmacol. Exp. Ther. 350, 646–656 (2014)CrossRefPubMed
63.
C.-W. Chen, R.P. Koche, A.U. Sinha, A.J. Deshpande, N. Zhu, R. Eng, J.G. Doench, H. Xu, S.H. Chu, J. Qi, X. Wang, C. Delaney, K.M. Bernt, D.E. Root, W.C. Hahn, J.E. Bradner, S.A. Armstrong, DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia. Nat. Med. 21, 335–343 (2015)CrossRefPubMedPubMedCentral
64.
A. Hilfiker, D. Hilfiker-Kleiner, A. Pannuti, J.C. Lucchesi, mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes and to the SAS genes of yeast, is required for dosage compensation in Drosophila. EMBO J. 16, 2054–2060 (1997)CrossRefPubMedPubMedCentral
65.
M. Taipale, S. Rea, K. Richter, A. Vilar, P. Lichter, A. Imhof, A. Akhtar, hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells. Mol. Cell. Biol. 25, 6798–6810 (2005)CrossRefPubMedPubMedCentral
66.
D.G. Valerio, H. Xu, C.-W. Chen, T. Hoshii, M.E. Eisold, C. Delaney, M. Cusan, A.J. Deshpande, C.-H. Huang, A. Lujambio, Y.G. Zheng, J. Zuber, T.K. Pandita, S.W. Lowe, S.A. Armstrong, Histone Acetyltransferase Activity of MOF Is Required for MLL-AF9 Leukemogenesis. Cancer Res. 77, 1753–1762 (2017)CrossRefPubMedPubMedCentral
67.
Y. Dou, T.A. Milne, A.J. Tackett, E.R. Smith, A. Fukuda, J. Wysocka, C.D. Allis, B.T. Chait, J.L. Hess, R.G. Roeder, Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 121, 873–885 (2005)CrossRefPubMed
68.
69.
F.W. Schmitges, A.B. Prusty, M. Faty, A. Stützer, G.M. Lingaraju, J. Aiwazian, R. Sack, D. Hess, L. Li, S. Zhou, R.D. Bunker, U. Wirth, T. Bouwmeester, A. Bauer, N. Ly-Hartig, K. Zhao, H. Chan, J. Gu, H. Gut, W. Fischle, J. Müller, N.H. Thomä, Histone methylation by PRC2 is inhibited by active chromatin marks. Mol. Cell 42, 330–341 (2011)CrossRefPubMed
70.
I.J. Majewski, M.E. Blewitt, C.A. de Graaf, E.J. McManus, M. Bahlo, A.A. Hilton, C.D. Hyland, G.K. Smyth, J.E. Corbin, D. Metcalf, W.S. Alexander, D.J. Hilton, Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity. PLoS Biol. 6, e93 (2008)CrossRefPubMedPubMedCentral
71.
S.C.W. Lee, S. Miller, C. Hyland, M. Kauppi, M. Lebois, L. Di Rago, D. Metcalf, S.A. Kinkel, E.C. Josefsson, M.E. Blewitt, I.J. Majewski, W.S. Alexander, Polycomb repressive complex 2 component Suz12 is required for hematopoietic stem cell function and lymphopoiesis. Blood 126, 167–175 (2015)CrossRefPubMed
72.
W. Yu, F. Zhang, S. Wang, Y. Fu, J. Chen, X. Liang, H. Le, W.T. Pu, B. Zhang, Depletion of polycomb repressive complex 2 core component EED impairs fetal hematopoiesis. Cell Death Dis. 8, e2744 (2017)CrossRefPubMedPubMedCentral
73.
H. Xie, J. Xu, J.H. Hsu, M. Nguyen, Y. Fujiwara, C. Peng, S.H. Orkin, Polycomb repressive complex 2 regulates normal hematopoietic stem cell function in a developmental-stage-specific manner. Cell Stem Cell 14, 68–80 (2014)CrossRefPubMed
74.
M. Mochizuki-Kashio, Y. Mishima, S. Miyagi, M. Negishi, A. Saraya, T. Konuma, J. Shinga, H. Koseki, A. Iwama, Dependency on the polycomb gene Ezh2 distinguishes fetal from adult hematopoietic stem cells. Blood 118, 6553–6561 (2011)CrossRefPubMed
75.
M. Mochizuki-Kashio, K. Aoyama, G. Sashida, M. Oshima, T. Tomioka, T. Muto, C. Wang, A. Iwama, Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous malignancies in an Ezh1-dependent manner. Blood 126, 1172–1183 (2015)CrossRefPubMed
76.
J. Shi, E. Wang, J. Zuber, A. Rappaport, M. Taylor, C. Johns, S.W. Lowe, C.R. Vakoc, The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;Nras(G12D) acute myeloid leukemia. Oncogene 32, 930–938 (2013)CrossRefPubMed
77.
W. Qi, K. Zhao, J. Gu, Y. Huang, Y. Wang, H. Zhang, M. Zhang, J. Zhang, Z. Yu, L. Li, L. Teng, S. Chuai, C. Zhang, M. Zhao, H. Chan, Z. Chen, D. Fang, Q. Fei, L. Feng, L. Feng, Y. Gao, H. Ge, X. Ge, G. Li, A. Lingel, Y. Lin, Y. Liu, F. Luo, M. Shi, L. Wang, Z. Wang, Y. Yu, J. Zeng, C. Zeng, L. Zhang, Q. Zhang, S. Zhou, C. Oyang, P. Atadja, E. Li, An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED. Nat. Chem. Biol. 13, 381–388 (2017)CrossRefPubMed
78.
Y. He, S. Selvaraju, M.L. Curtin, C.G. Jakob, H. Zhu, K.M. Comess, B. Shaw, J. The, E. Lima-Fernandes, M.M. Szewczyk, D. Cheng, K.L. Klinge, H.-Q. Li, M. Pliushchev, M.A. Algire, D. Maag, J. Guo, J. Dietrich, S.C. Panchal, A.M. Petros, R.F. Sweis, M. Torrent, L.J. Bigelow, G. Senisterra, F. Li, S. Kennedy, Q. Wu, D.J. Osterling, D.J. Lindley, W. Gao, S. Galasinski, D. Barsyte-Lovejoy, M. Vedadi, F.G. Buchanan, C.H. Arrowsmith, G.G. Chiang, C. Sun, W.N. Pappano, The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat. Chem. Biol. 13, 389–395 (2017)CrossRefPubMed
79.
B. Xu, D.M. On, A. Ma, T. Parton, K.D. Konze, S.G. Pattenden, D.F. Allison, L. Cai, S. Rockowitz, S. Liu, Y. Liu, F. Li, M. Vedadi, S.V. Frye, B.A. Garcia, D. Zheng, J. Jin, G.G. Wang, Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood 125, 346–357 (2015)CrossRefPubMedPubMedCentral
80.
D. Honma, O. Kanno, J. Watanabe, J. Kinoshita, M. Hirasawa, E. Nosaka, M. Shiroishi, T. Takizawa, I. Yasumatsu, T. Horiuchi, A. Nakao, K. Suzuki, T. Yamasaki, K. Nakajima, M. Hayakawa, T. Yamazaki, A.S. Yadav, N. Adachi, Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor. Cancer Sci. 108, 2069–2078 (2017)CrossRefPubMedPubMedCentral
81.
I. Pinheiro, R. Margueron, N. Shukeir, M. Eisold, C. Fritzsch, F.M. Richter, G. Mittler, C. Genoud, S. Goyama, M. Kurokawa, J. Son, D. Reinberg, M. Lachner, T. Jenuwein, Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell 150, 948–960 (2012)CrossRefPubMed
82.
F. Aguilo, S. Avagyan, A. Labar, A. Sevilla, D.-F. Lee, P. Kumar, I.R. Lemischka, B.Y. Zhou, H.-W. Snoeck, Prdm16 is a physiologic regulator of hematopoietic stem cells. Blood 117, 5057–5066 (2011)CrossRefPubMedPubMedCentral
83.
E. Deneault, S. Cellot, A. Faubert, J.-P. Laverdure, M. Fréchette, J. Chagraoui, N. Mayotte, M. Sauvageau, S.B. Ting, G. Sauvageau, A functional screen to identify novel effectors of hematopoietic stem cell activity. Cell 137, 369–379 (2009)CrossRefPubMedPubMedCentral
84.
I. Nishikata, H. Sasaki, M. Iga, Y. Tateno, S. Imayoshi, N. Asou, T. Nakamura, K. Morishita, A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation. Blood 102, 3323–3332 (2003)CrossRefPubMed
85.
D.C. Shing, M. Trubia, F. Marchesi, E. Radaelli, E. Belloni, C. Tapinassi, E. Scanziani, C. Mecucci, B. Crescenzi, I. Lahortiga, M.D. Odero, G. Zardo, A. Gruszka, S. Minucci, P.P. Di Fiore, P.G. Pelicci, Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in mice. J. Clin. Invest. 117, 3696–3707 (2007)PubMedPubMedCentral
86.
I. Sakai, T. Tamura, H. Narumi, N. Uchida, Y. Yakushijin, T. Hato, S. Fujita, M. Yasukawa, Novel RUNX1-PRDM16 fusion transcripts in a patient with acute myeloid leukemia showing t(1;21)(p36;q22). Genes Chromosom. Cancer 44, 265–270 (2005)CrossRefPubMed
87.
C. Roche-Lestienne, L. Deluche, S. Corm, I. Tigaud, S. Joha, N. Philippe, S. Geffroy, J.-L. Laï, F.-E. Nicolini, C. Preudhomme, RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance. Blood 111, 3735–3741 (2008)CrossRefPubMed
88.
B.D. Strahl, S.D. Briggs, C.J. Brame, J.A. Caldwell, S.S. Koh, H. Ma, R.G. Cook, J. Shabanowitz, D.F. Hunt, M.R. Stallcup, C.D. Allis, Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1. Curr. Biol. 11, 996–1000 (2001)CrossRefPubMed
89.
T.L. Branscombe, A. Frankel, J.H. Lee, J.R. Cook, Z. Yang, S. Pestka, S. Clarke, PRMT5 (Janus kinase-binding protein 1) catalyzes the formation of symmetric dimethylarginine residues in proteins. J. Biol. Chem. 276, 32971–32976 (2001)CrossRefPubMed
90.
F. Liu, G. Cheng, P.-J. Hamard, S. Greenblatt, L. Wang, N. Man, F. Perna, H. Xu, M. Tadi, L. Luciani, S.D. Nimer, Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis. J. Clin. Invest. 125, 3532–3544 (2015)CrossRefPubMedPubMedCentral
91.
J. Serio, J. Ropa, W. Chen, M. Mysliwski, N. Saha, L. Chen, J. Wang, H. Miao, T. Cierpicki, J. Grembecka, A.G. Muntean, The PAF complex regulation of Prmt5 facilitates the progression and maintenance of MLL fusion leukemia. Oncogene 37, 450–460 (2018)CrossRefPubMed
92.
J.W. Edmunds, L.C. Mahadevan, A.L. Clayton, Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation. EMBO J. 27, 406–420 (2008)CrossRefPubMed
93.
Y.-L. Zhang, J.-W. Sun, Y.-Y. Xie, Y. Zhou, P. Liu, J.-C. Song, C.-H. Xu, L. Wang, D. Liu, A.-N. Xu, Z. Chen, S.-J. Chen, X.-J. Sun, Q.-H. Huang, Setd2 deficiency impairs hematopoietic stem cell self-renewal and causes malignant transformation. Cell Res. 28, 476–490 (2018)CrossRefPubMedPubMedCentral
94.
X. Zhu, F. He, H. Zeng, S. Ling, A. Chen, Y. Wang, X. Yan, W. Wei, Y. Pang, H. Cheng, C. Hua, Y. Zhang, X. Yang, X. Lu, L. Cao, L. Hao, L. Dong, W. Zou, J. Wu, X. Li, S. Zheng, J. Yan, J. Zhou, L. Zhang, S. Mi, X. Wang, L. Zhang, Y. Zou, Y. Chen, Z. Geng, J. Wang, J. Zhou, X. Liu, J. Wang, W. Yuan, G. Huang, T. Cheng, Q.-F. Wang, Identification of functional cooperative mutations of SETD2 in human acute leukemia. Nat. Genet. 46, 287–293 (2014)CrossRefPubMedPubMedCentral
95.
Y. Shi, F. Lan, C. Matson, P. Mulligan, J.R. Whetstine, P.A. Cole, R.A. Casero, Y. Shi, Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119, 941–953 (2004)CrossRefPubMed
96.
A. Sprüssel, J.H. Schulte, S. Weber, M. Necke, K. Händschke, T. Thor, K.W. Pajtler, A. Schramm, K. König, L. Diehl, P. Mestdagh, J. Vandesompele, F. Speleman, H. Jastrow, L.C. Heukamp, R. Schüle, U. Dührsen, R. Buettner, A. Eggert, J.R. Göthert, Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation. Leukemia 26, 2039–2051 (2012)CrossRefPubMed
97.
J.P. McGrath, K.E. Williamson, S. Balasubramanian, S. Odate, S. Arora, C. Hatton, T.M. Edwards, T. O'Brien, S. Magnuson, D. Stokoe, D.L. Daniels, B.M. Bryant, P. Trojer, Pharmacological inhibition of the histone lysine demethylase KDM1A suppresses the growth of multiple acute myeloid eukemia subtypes. Cancer Res. 76, 1975–1988 (2016)CrossRefPubMed
98.
Y.-i. Tsukada, J. Fang, H. Erdjument-Bromage, M.E. Warren, C.H. Borchers, P. Tempst, Y. Zhang, Histone demethylation by a family of JmjC domain-containing proteins. Nature 439, 811–816 (2006)CrossRefPubMed
99.
M. Brauchle, Z. Yao, R. Arora, S. Thigale, I. Clay, B. Inverardi, J. Fletcher, P. Taslimi, M.G. Acker, B. Gerrits, J. Voshol, A. Bauer, D. Schübeler, T. Bouwmeester, H. Ruffner, Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation. PLoS ONE 8, e60549 (2013)CrossRefPubMedPubMedCentral
100.
M. Katoh, M. Katoh, Comparative integromics on JMJD1C gene encoding histone demethylase: Conserved POU5F1 binding site elucidating mechanism of JMJD1C expression in undifferentiated ES cells and diffuse-type gastric cancer. Int. J. Oncol. 31, 219–223 (2007)PubMed
101.
P.A.C. Cloos, J. Christensen, K. Agger, A. Maiolica, J. Rappsilber, T. Antal, K.H. Hansen, K. Helin, The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3. Nature 442, 307–311 (2006)CrossRefPubMed
102.
D.J. Seward, G. Cubberley, S. Kim, M. Schonewald, L. Zhang, B. Tripet, D.L. Bentley, Demethylation of trimethylated histone H3 Lys4 in vivo by JARID1 JmjC proteins. Nat. Struct. Mol. Biol. 14, 240–242 (2007)CrossRefPubMed
103.
S. Cellot, K.J. Hope, J. Chagraoui, M. Sauvageau, É. Deneault, T. MacRae, N. Mayotte, B.T. Wilhelm, J.R. Landry, S.B. Ting, J. Krosl, K. Humphries, A. Thompson, G. Sauvageau, RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity. Blood 122, 1545–1555 (2013)CrossRefPubMed
104.
M.H. Stewart, M. Albert, P. Sroczynska, V.A. Cruickshank, Y. Guo, D.J. Rossi, K. Helin, T. Enver, The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal in mice. Blood 125, 2075–2078 (2015)CrossRefPubMedPubMedCentral
105.
R.B. Lorsbach, J. Moore, S. Mathew, S.C. Raimondi, S.T. Mukatira, J.R. Downing, TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia 17, 637–641 (2003)CrossRefPubMed
106.
J.U. Guo, Y. Su, C. Zhong, G.-l. Ming, H. Song, Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145, 423–434 (2011)CrossRefPubMedPubMedCentral
107.
A.J. Stonestrom, S.C. Hsu, K.S. Jahn, P. Huang, C.A. Keller, B.M. Giardine, S. Kadauke, A.E. Campbell, P. Evans, R.C. Hardison, G.A. Blobel, Functions of BET proteins in erythroid gene expression. Blood 125, 2825–2834 (2015)CrossRefPubMedPubMedCentral
108.
R.M. Rodriguez, B. Suarez-Alvarez, R. Salvanés, C. Huidobro, E.G. Toraño, J.L. Garcia-Perez, C. Lopez-Larrea, A.F. Fernandez, C. Bueno, P. Menendez, M.F. Fraga, Role of BRD4 in hematopoietic differentiation of embryonic stem cells. Epigenetics 9, 566–578 (2014)CrossRefPubMedPubMedCentral
109.
M.A. Dawson, R.K. Prinjha, A. Dittmann, G. Giotopoulos, M. Bantscheff, W.-I. Chan, S.C. Robson, C.-w. Chung, C. Hopf, M.M. Savitski, C. Huthmacher, E. Gudgin, D. Lugo, S. Beinke, T.D. Chapman, E.J. Roberts, P.E. Soden, K.R. Auger, O. Mirguet, K. Doehner, R. Delwel, A.K. Burnett, P. Jeffrey, G. Drewes, K. Lee, B.J.P. Huntly, T. Kouzarides, Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 478, 529–533 (2011)CrossRefPubMedPubMedCentral
110.
A. Chaidos, V. Caputo, A. Karadimitris, Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence. Ther Adv Hematol 6, 128–141 (2015)CrossRefPubMedPubMedCentral
111.
K. Klauke, V. Radulović, M. Broekhuis, E. Weersing, E. Zwart, S. Olthof, M. Ritsema, S. Bruggeman, X. Wu, K. Helin, L. Bystrykh, G. de Haan, Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation. Nat. Cell Biol. 15, 353–362 (2013)CrossRefPubMed
112.
E. Maethner, M.-P. Garcia-Cuellar, C. Breitinger, S. Takacova, V. Divoky, J.L. Hess, R.K. Slany, MLL-ENL inhibits polycomb repressive complex 1 to achieve efficient transformation of hematopoietic cells. Cell Rep. 3, 1553–1566 (2013)CrossRefPubMedPubMedCentral
113.
C.S. Hemenway, A.C. de Erkenez, G.C. Gould, The polycomb protein MPc3 interacts with AF9, an MLL fusion partner in t(9;11)(p22;q23) acute leukemias. Oncogene 20, 3798–3805 (2001)CrossRefPubMed
114.
H. Méreau, J. de Rijck, K. Cermáková, A. Kutz, S. Juge, J. Demeulemeester, R. Gijsbers, F. Christ, Z. Debyser, J. Schwaller, Impairing MLL-fusion gene-mediated transformation by dissecting critical interactions with the lens epithelium-derived growth factor (LEDGF/p75). Leukemia 27, 1245–1253 (2013)CrossRefPubMed
115.
K. Cermáková, P. Tesina, J. Demeulemeester, S. El Ashkar, H. Méreau, J. Schwaller, P. Rezáčová, V. Veverka, J. de Rijck, Validation and structural characterization of the LEDGF/p75-MLL interface as a new target for the treatment of MLL-dependent leukemia. Cancer Res. 74, 5139–5151 (2014)CrossRefPubMed
116.
M.J. Murai, J. Pollock, S. He, H. Miao, T. Purohit, A. Yokom, J.L. Hess, A.G. Muntean, J. Grembecka, T. Cierpicki, The same site on the integrase-binding domain of lens epithelium-derived growth factor is a therapeutic target for MLL leukemia and HIV. Blood 124, 3730–3737 (2014)CrossRefPubMedPubMedCentral
117.
Y.-X. Chen, J. Yan, K. Keeshan, A.T. Tubbs, H. Wang, A. Silva, E.J. Brown, J.L. Hess, W.S. Pear, X. Hua, The tumor suppressor menin regulates hematopoiesis and myeloid transformation by influencing Hox gene expression. Proc. Natl. Acad. Sci. U. S. A. 103, 1018–1023 (2006)CrossRefPubMedPubMedCentral
118.
E. Novotny, S. Compton, P.P. Liu, F.S. Collins, S.C. Chandrasekharappa, In vitro hematopoietic differentiation of mouse embryonic stem cells requires the tumor suppressor menin and is mediated by Hoxa9. Mech. Dev. 126, 517–522 (2009)CrossRefPubMedPubMedCentral
119.
I. Maillard, Y.-X. Chen, A. Friedman, Y. Yang, A.T. Tubbs, O. Shestova, W.S. Pear, X. Hua, Menin regulates the function of hematopoietic stem cells and lymphoid progenitors. Blood 113, 1661–1669 (2009)CrossRefPubMedPubMedCentral
120.
S. Jin, H. Zhao, Y. Yi, Y. Nakata, A. Kalota, A.M. Gewirtz, c-Myb binds MLL through menin in human leukemia cells and is an important driver of MLL-associated leukemogenesis. J. Clin. Invest. 120, 593–606 (2010)CrossRefPubMedPubMedCentral
121.
J. Grembecka, S. He, A. Shi, T. Purohit, A.G. Muntean, R.J. Sorenson, H.D. Showalter, M.J. Murai, A.M. Belcher, T. Hartley, J.L. Hess, T. Cierpicki, Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nat. Chem. Biol. 8, 277–284 (2012)CrossRefPubMedPubMedCentral
122.
D. Borkin, S. He, H. Miao, K. Kempinska, J. Pollock, J. Chase, T. Purohit, B. Malik, T. Zhao, J. Wang, B. Wen, H. Zong, M. Jones, G. Danet-Desnoyers, M.L. Guzman, M. Talpaz, D.L. Bixby, D. Sun, J.L. Hess, A.G. Muntean, I. Maillard, T. Cierpicki, J. Grembecka, Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell 27, 589–602 (2015)CrossRefPubMedPubMedCentral
123.
S. He, B. Malik, D. Borkin, H. Miao, S. Shukla, K. Kempinska, T. Purohit, J. Wang, L. Chen, B. Parkin, S.N. Malek, G. Danet-Desnoyers, A.G. Muntean, T. Cierpicki, J. Grembecka, Menin-MLL inhibitors block oncogenic transformation by MLL-fusion proteins in a fusion partner-independent manner. Leukemia 30, 508–513 (2016)CrossRefPubMed
124.
E. Shema, I. Tirosh, Y. Aylon, J. Huang, C. Ye, N. Moskovits, N. Raver-Shapira, N. Minsky, J. Pirngruber, G. Tarcic, P. Hublarova, L. Moyal, M. Gana-Weisz, Y. Shiloh, Y. Yarden, S.A. Johnsen, B. Vojtesek, S.L. Berger, M. Oren, The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression. Genes Dev. 22, 2664–2676 (2008)CrossRefPubMedPubMedCentral
125.
A.S. Advani, C-kit as a target in the treatment of acute myelogenous leukemia. Curr Hematol Rep 4, 51–58 (2005)PubMed
126.
P. Rathert, M. Roth, T. Neumann, F. Muerdter, J.-S. Roe, M. Muhar, S. Deswal, S. Cerny-Reiterer, B. Peter, J. Jude, T. Hoffmann, Ł.M. Boryń, E. Axelsson, N. Schweifer, U. Tontsch-Grunt, L.E. Dow, D. Gianni, M. Pearson, P. Valent, A. Stark, N. Kraut, C.R. Vakoc, J. Zuber, Transcriptional plasticity promotes primary and acquired resistance to BET inhibition. Nature 525, 543–547 (2015)CrossRefPubMedPubMedCentral
127.
O. Gilan, E.Y.N. Lam, I. Becher, D. Lugo, E. Cannizzaro, G. Joberty, A. Ward, M. Wiese, C.Y. Fong, S. Ftouni, D. Tyler, K. Stanley, L. MacPherson, C.-F. Weng, Y.-C. Chan, M. Ghisi, D. Smil, C. Carpenter, P. Brown, N. Garton, M.E. Blewitt, A.J. Bannister, T. Kouzarides, B.J.P. Huntly, R.W. Johnstone, G. Drewes, S.-J. Dawson, C.H. Arrowsmith, P. Grandi, R.K. Prinjha, M.A. Dawson, Functional interdependence of BRD4 and DOT1L in MLL leukemia. Nat. Struct. Mol. Biol. 23, 673–681 (2016)CrossRefPubMed
128.
H. Okuda, B. Stanojevic, A. Kanai, T. Kawamura, S. Takahashi, H. Matsui, A. Takaori-Kondo, A. Yokoyama, Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia. J. Clin. Invest. 127, 1918–1931 (2017)CrossRefPubMedPubMedCentral
129.
C. Dafflon, V.J. Craig, H. Méreau, J. Gräsel, B. Schacher Engstler, G. Hoffman, F. Nigsch, S. Gaulis, L. Barys, M. Ito, J. Aguadé-Gorgorió, B. Bornhauser, J.-P. Bourquin, A. Proske, C. Stork-Fux, M. Murakami, W.R. Sellers, F. Hofmann, J. Schwaller, R. Tiedt, Complementary activities of DOT1L and Menin inhibitors in MLL-rearranged leukemia. Leukemia 31, 1269–1277 (2017)CrossRefPubMed
130.
M.W.M. Kühn, E. Song, Z. Feng, A. Sinha, C.-W. Chen, A.J. Deshpande, M. Cusan, N. Farnoud, A. Mupo, C. Grove, R. Koche, J.E. Bradner, E. de Stanchina, G.S. Vassiliou, T. Hoshii, S.A. Armstrong, Targeting Chromatin regulators inhibits leukemogenic gene expression in NPM1 mutant leukemia. Cancer Discov. 6, 1166–1181 (2016)CrossRefPubMedPubMedCentral
131.
132.
S.X. Pfister, A. Ashworth, Marked for death: targeting epigenetic changes in cancer. Nat. Rev. Drug Discov. 16, 241–263 (2017)CrossRefPubMed
133.
A. Chavez-Gonzalez, B. Bakhshinejad, K. Pakravan, M.L. Guzman, S. Babashah, Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer. Cell. Oncol. 40, 1–20 (2017)CrossRef
134.
I.A. Voutsadakis, Expression and function of immune ligand-receptor pairs in NK cells and cancer stem cells: therapeutic implications. Cell. Oncol. 41, 107–121 (2018)CrossRef
135.
P. Gotwals, S. Cameron, D. Cipolletta, V. Cremasco, A. Crystal, B. Hewes, B. Mueller, S. Quaratino, C. Sabatos-Peyton, L. Petruzzelli, J.A. Engelman, G. Dranoff, Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat. Rev. Cancer 17, 286–301 (2017)CrossRefPubMed
Metadata
Title
Therapeutic targeting potential of chromatin-associated proteins in MLL-rearranged acute leukemia
Authors
Xin Xu
Björn Schneider
Publication date
01-04-2019
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 2/2019
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-018-0414-4

Other articles of this Issue 2/2019

Cellular Oncology 2/2019 Go to the issue

Original Article

Interfering with bromodomain epigenome readers as therapeutic option in mucoepidermoid carcinoma

Review

MicroRNA-mediated redox regulation modulates therapy resistance in cancer cells: clinical perspectives

Original Paper

Antitumor effect of XCT790, an ERRα inverse agonist, on ERα-negative endometrial cancer cells

Original Paper

Nanoquinacrine sensitizes 5-FU-resistant cervical cancer stem-like cells by down-regulating Nectin-4 via ADAM-17 mediated NOTCH deregulation

Commentary

Nuclear localization of PD-L1: artifact or reality?

Original Paper

Concomitant dysregulation of the estrogen receptor and BRAF/MEK signaling pathways is common in colorectal cancer and predicts a worse prognosis
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