SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance

被引：22

作者：

Cruickshank, V. Adam ^{[1
,2
]}

Sroczynska, Patrycja ^{[1
,2
]}

Sankar, Aditya ^{[1
,2
]}

Miyagi, Satoru ^{[1
,2
,3
]}

Rundsten, Carsten Friis ^{[1
]}

Johansen, Jens Vilstrup ^{[1
]}

Helin, Kristian ^{[1
,2
,3
]}

机构：

[1] Univ Copenhagen, BRIC, DK-2200 Copenhagen, Denmark

[2] Univ Copenhagen, Ctr Epigenet, DK-2200 Copenhagen, Denmark

[3] Univ Copenhagen, Danish Stem Cell Ctr Danstem, DK-2200 Copenhagen, Denmark

来源：

PLOS ONE | 2015年 / 10卷 / 11期

基金：

英国医学研究理事会; 新加坡国家研究基金会;

关键词：

METHYLTRANSFERASE GENE EZH2; INACTIVATING MUTATIONS; DNMT3A MUTATIONS; CHROMATIN; BRG1; TET2; EXPRESSION; COMPLEX; TARGET;

D O I：

10.1371/journal.pone.0142806

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Alterations in chromatin structure caused by deregulated epigenetic mechanisms collaborate with underlying genetic lesions to promote cancer. SMARCA4/BRG1, a core component of the SWI/SNF ATP-dependent chromatin-remodelling complex, has been implicated by its mutational spectrum as exerting a tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the three proteins demonstrate that they are required for the expression of haematopoietic stem cell associated genes but in contrast to previous results obtained in mouse cells, the three proteins are not required for the expression of c-MYC regulated genes.

引用

页数：13

共 37 条

[1] Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies [J].

Abdel-Wahab, Omar ;

Mullally, Ann ;

Hedvat, Cyrus ;

Garcia-Manero, Guillermo ;

Patel, Jay ;

Wadleigh, Martha ;

Malinge, Sebastien ;

Yao, JinJuan ;

Kilpivaara, Outi ;

Bhat, Rukhmi ;

Huberman, Kety ;

Thomas, Sabrena ;

Dolgalev, Igor ;

Heguy, Adriana ;

Paietta, Elisabeth ;

Le Beau, Michelle M. ;

Beran, Miloslav ;

Tallman, Martin S. ;

Ebert, Benjamin L. ;

Kantarjian, Hagop M. ;

Stone, Richard M. ;

Gilliland, D. Gary ;

Crispino, John D. ;

Levine, Ross L. .

BLOOD, 2009, 114 (01) :144-147

[2] Implications of NRAS mutations in AML:: a study of 2502 patients [J].

Bacher, Ulrike ;

Haferlach, Torsten ;

Schoch, Claudia ;

Kern, Wolfgang ;

Schnittger, Susanne .

BLOOD, 2006, 107 (10) :3847-3853

[3] The SWIB and the MDM2 domains are homologous and share a common fold [J].

Bennett-Lovsey, R ;

Hart, SE ;

Shirai, H ;

Mizuguchi, K .

BIOINFORMATICS, 2002, 18 (04) :626-630

[4] A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes [J].

Bultman, S ;

Gebuhr, T ;

Yee, D ;

La Mantia, C ;

Nicholson, J ;

Gilliam, A ;

Randazzo, F ;

Metzger, D ;

Chambon, P ;

Crabtree, G ;

Magnuson, T .

MOLECULAR CELL, 2000, 6 (06) :1287-1295

[5] Essential role of BRG, the ATPase subunit of BAF chromatin remodeling complexes, in leukemia maintenance [J].

Buscarlet, Manuel ;

Krasteva, Veneta ;

Ho, Lena ;

Simon, Camille ;

Hebert, Josee ;

Wilhelm, Brian ;

Crabtree, Gerald R. ;

Sauvageau, Guy ;

Thibault, Pierre ;

Lessard, Julie A. .

BLOOD, 2014, 123 (11) :1720-1728

[6] Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia [J].

Dawson, Mark A. ;

Prinjha, Rab K. ;

Dittmann, Antje ;

Giotopoulos, George ;

Bantscheff, Marcus ;

Chan, Wai-In ;

Robson, Samuel C. ;

Chung, Chun-wa ;

Hopf, Carsten ;

Savitski, Mikhail M. ;

Huthmacher, Carola ;

Gudgin, Emma ;

Lugo, Dave ;

Beinke, Soren ;

Chapman, Trevor D. ;

Roberts, Emma J. ;

Soden, Peter E. ;

Auger, Kurt R. ;

Mirguet, Olivier ;

Doehner, Konstanze ;

Delwel, Ruud ;

Burnett, Alan K. ;

Jeffrey, Phillip ;

Drewes, Gerard ;

Lee, Kevin ;

Huntly, Brian J. P. ;

Kouzarides, Tony .

NATURE, 2011, 478 (7370) :529-533

[7] Mutation in TET2 in Myeloid Cancers [J].

Delhommeau, Francois ;

Dupont, Sabrina ;

Della Valle, Veronique ;

James, Chloe ;

Trannoy, Severine ;

Masse, Aline ;

Kosmider, Olivier ;

Le Couedic, Jean-Pierre ;

Robert, Fabienne ;

Alberdi, Antonio ;

Lecluse, Yann ;

Plo, Isabelle ;

Dreyfus, Francois J. ;

Marzac, Christophe ;

Casadevall, Nicole ;

Lacombe, Catherine ;

Romana, Serge P. ;

Dessen, Philippe ;

Soulier, Jean ;

Viguie, Franck ;

Fontenay, Michaela ;

Vainchenker, William ;

Bernard, Olivier A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (22) :2289-2301

[8] Chromatin modifications as therapeutic targets in MLL-rearranged leukemia [J].

Deshpande, Aniruddha J. ;

Bradner, James ;

Armstrong, Scott A. .

TRENDS IN IMMUNOLOGY, 2012, 33 (11) :563-570

[9] A somatic EZH2 mutation in childhood acute myeloid leukemia [J].

Ernst, T. ;

Pflug, A. ;

Rinke, J. ;

Ernst, J. ;

Bierbach, U. ;

Beck, J. F. ;

Hochhaus, A. ;

Gruhn, B. .

LEUKEMIA, 2012, 26 (07) :1701-1703

[10] Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders [J].

Ernst, Thomas ;

Chase, Andrew J. ;

Score, Joannah ;

Hidalgo-Curtis, Claire E. ;

Bryant, Catherine ;

Jones, Amy V. ;

Waghorn, Katherine ;

Zoi, Katerina ;

Ross, Fiona M. ;

Reiter, Andreas ;

Hochhaus, Andreas ;

Drexler, Hans G. ;

Duncombe, Andrew ;

Cervantes, Francisco ;

Oscier, David ;

Boultwood, Jacqueline ;

Grand, Francis H. ;

Cross, Nicholas C. P. .

NATURE GENETICS, 2010, 42 (08) :722-U109

← 1 2 3 4 →