EZH2 in normal hematopoiesis and hematological malignancies

被引：86

作者：

Herviou, Laurie ^{[2
]}

Cavalli, Giacomo ^{[2
]}

Cartron, Guillaume ^{[3
,4
]}

Klein, Bernard ^{[1
,2
,3
]}

Moreaux, Jerome ^{[1
,2
,3
]}

机构：

[1] CHU Montpellier, Dept Biol Hematol, Montpellier, France

[2] CNRS, Inst Human Genet, UPR1142, Montpellier, France

[3] Univ Montpellier I, UFR Med, Montpellier, France

[4] CHU Montpellier, Dept Clin Hematol, Montpellier, France

来源：

ONCOTARGET | 2016年 / 7卷 / 03期

关键词：

hematological malignancies; EZH2; Polycomb complex; therapeutic target; HISTONE METHYLTRANSFERASE EZH2; POLYCOMB-GROUP GENE; GROUP PROTEIN EZH2; B-CELL LYMPHOMAS; AGGRESSIVE BREAST-CANCER; REPRESSIVE COMPLEX 2; GERMINAL-CENTER; SOMATIC MUTATIONS; STEM-CELLS; SELECTIVE-INHIBITION;

D O I：

10.18632/oncotarget.6198

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2, inhibits gene expression through methylation on lysine 27 of histone H3. EZH2 regulates normal hematopoietic stem cell self-renewal and differentiation. EZH2 also controls normal B cell differentiation. EZH2 deregulation has been described in many cancer types including hematological malignancies. Specific small molecules have been recently developed to exploit the oncogenic addiction of tumor cells to EZH2. Their therapeutic potential is currently under evaluation. This review summarizes the roles of EZH2 in normal and pathologic hematological processes and recent advances in the development of EZH2 inhibitors for the personalized treatment of patients with hematological malignancies.

引用

页码：2284 / 2296

页数：13

共 101 条

[1] In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2 [J].

Abd Al Kader, Lamia ;

Oka, Takashi ;

Takata, Katsuyoshi ;

Sun, Xu ;

Sato, Hiaki ;

Murakami, Ichiro ;

Toji, Tomohiro ;

Manabe, Akihiro ;

Kimura, Hiroshi ;

Yoshino, Tadashi .

VIRCHOWS ARCHIV, 2013, 463 (05) :697-711

[2] ASXL1 Mutations Promote Myeloid Transformation through Loss of PRC2-Mediated Gene Repression [J].

Abdel-Wahab, Omar ;

Adli, Mazhar ;

LaFave, Lindsay M. ;

Gao, Jie ;

Hricik, Todd ;

Shih, Alan H. ;

Pandey, Suveg ;

Patel, Jay P. ;

Chung, Young Rock ;

Koche, Richard ;

Perna, Fabiana ;

Zhao, Xinyang ;

Taylor, Jordan E. ;

Park, Christopher Y. ;

Carroll, Martin ;

Melnick, Ari ;

Nimer, Stephen D. ;

Jaffe, Jacob D. ;

Aifantis, Iannis ;

Bernstein, Bradley E. ;

Levine, Ross L. .

CANCER CELL, 2012, 22 (02) :180-193

[3] Characterization of the EZH2-MMSET Histone Methyltransferase Regulatory Axis in Cancer [J].

Asangani, Irfan A. ;

Ateeq, Bushra ;

Cao, Qi ;

Dodson, Lois ;

Pandhi, Mithil ;

Kunju, Lakshmi P. ;

Mehra, Rohit ;

Lonigro, Robert J. ;

Siddiqui, Javed ;

Palanisamy, Nallasivam ;

Wu, Yi-Mi ;

Cao, Xuhong ;

Kim, Jung H. ;

Zhao, Meng ;

Qin, Zhaohui S. ;

Iyer, Mathew K. ;

Maher, Christopher A. ;

Kumar-Sinha, Chandan ;

Varambally, Sooryanarayana ;

Chinnaiyan, Arul M. .

MOLECULAR CELL, 2013, 49 (01) :80-93

[4] High-resolution profiling of histone methylations in the human genome [J].

Barski, Artern ;

Cuddapah, Suresh ;

Cui, Kairong ;

Roh, Tae-Young ;

Schones, Dustin E. ;

Wang, Zhibin ;

Wei, Gang ;

Chepelev, Iouri ;

Zhao, Keji .

CELL, 2007, 129 (04) :823-837

[5] Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes [J].

Baxter, J ;

Sauer, S ;

Peters, A ;

John, R ;

Williams, R ;

Caparros, ML ;

Arney, K ;

Otte, A ;

Jenuwein, T ;

Merkenschlager, M ;

Fisher, AG .

EMBO JOURNAL, 2004, 23 (22) :4462-4472

[6] EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation [J].

Beguelin, Wendy ;

Popovic, Relja ;

Teater, Matt ;

Jiang, Yanwen ;

Bunting, Karen L. ;

Rosen, Monica ;

Shen, Hao ;

Yang, Shao Ning ;

Wang, Ling ;

Ezponda, Teresa ;

Martinez-Garcia, Eva ;

Zhang, Haikuo ;

Zheng, Yupeng ;

Verma, Sharad K. ;

McCabe, Michael T. ;

Ott, Heidi M. ;

Van Aller, Glenn S. ;

Kruger, Ryan G. ;

Liu, Yan ;

McHugh, Charles F. ;

Scott, David W. ;

Chung, Young Rock ;

Kelleher, Neil ;

Shaknovich, Rita ;

Creasy, Caretha L. ;

Gascoyne, Randy D. ;

Wong, Kwok-Kin ;

Cerchietti, Leandro ;

Levine, Ross L. ;

Abdel-Wahab, Omar ;

Licht, Jonathan D. ;

Elemento, Olivier ;

Melnick, Ari M. .

CANCER CELL, 2013, 23 (05) :677-692

[7] A transgenic mouse model demonstrating the oncogenic role of mutations in the polycomb-group gene EZH2 in lymphomagenesis [J].

Berg, Tobias ;

Thoene, Silvia ;

Yap, Damian ;

Wee, Tracee ;

Schoeler, Nathalie ;

Rosten, Patty ;

Lim, Emilia ;

Bilenky, Misha ;

Mungall, Andrew J. ;

Oellerich, Thomas ;

Lee, Sherry ;

Lai, Courteney K. ;

Umlandt, Patricia ;

Salmi, Anisa ;

Chang, Harry ;

Yue, Lisa ;

Lai, David ;

Cheng, S-W Grace ;

Morin, Ryan D. ;

Hirst, Martin ;

Serve, Hubert ;

Marra, Marco A. ;

Morin, Gregg B. ;

Gascoyne, Randy D. ;

Aparicio, Samuel A. ;

Humphries, R. Keith .

BLOOD, 2014, 123 (25) :3914-3924

[8] Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation [J].

Blackledge, Neil P. ;

Farcas, Anca M. ;

Kondo, Takashi ;

King, Hamish W. ;

McGouran, Joanna F. ;

Hanssen, Lars L. P. ;

Ito, Shinsuke ;

Cooper, Sarah ;

Kondo, Kaori ;

Koseki, Yoko ;

Ishikura, Tomoyuki ;

Long, Hannah K. ;

Sheahan, Thomas W. p ;

Brockdorff, Neil ;

Kessler, Benedikt M. ;

Koseki, Haruhiko ;

Klose, Robert J. .

CELL, 2014, 157 (06) :1445-1459

[9] EZH2 Y641 mutations in follicular lymphoma [J].

Boedoer, C. ;

O'Riain, C. ;

Wrench, D. ;

Matthews, J. ;

Iyengar, S. ;

Tayyib, H. ;

Calaminici, M. ;

Clear, A. ;

Iqbal, S. ;

Quentmeier, H. ;

Drexler, H. G. ;

Montoto, S. ;

Lister, A. T. ;

Gribben, J. G. ;

Matolcsy, A. ;

Fitzgibbon, J. .

LEUKEMIA, 2011, 25 (04) :726-729

[10] EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer [J].

Adrian P. Bracken ;

Diego Pasini ;

Maria Capra ;

Elena Prosperini ;

Elena Colli ;

Kristian Helin .

The EMBO Journal, 2003, 22 (20) :5323-5335

← 1 2 3 4 5 6 7 8 9 10 →