Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma

被引：379

作者：

Hashizume, Rintaro ^{[1
]}

Andor, Noemi ^{[2
]}

Ihara, Yuichiro ^{[2
]}

Lerner, Robin ^{[2
]}

Gan, Haiyun ^{[3
]}

Chen, Xiaoyue ^{[3
]}

Fang, Dong ^{[3
]}

Huang, Xi ^{[4
]}

Tom, Maxwell W. ^{[2
]}

Ngo, Vy ^{[5
]}

Solomon, David ^{[6
,7
]}

Mueller, Sabine ^{[2
,8
,9
]}

Paris, Pamela L. ^{[5
]}

Zhang, Zhiguo ^{[3
]}

Petritsch, Claudia ^{[2
]}

Gupta, Nalin ^{[2
]}

Waldman, Todd A. ^{[7
]}

James, C. David ^{[1
]}

机构：

[1] Northwestern Univ, Dept Neurol Surg, Feinberg Sch Med, Chicago, IL 60611 USA

[2] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

[3] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN USA

[4] Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA

[5] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA

[6] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA

[7] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Washington, DC USA

[8] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA

[9] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA

来源：

NATURE MEDICINE | 2014年 / 20卷 / 12期

基金：

美国国家卫生研究院;

关键词：

HIGH-GRADE GLIOMAS; GENE-EXPRESSION; GLIOBLASTOMA; METHYLATION; MUTATIONS; H3K27ME3; EZH2;

D O I：

10.1038/nm.3716

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3.3. Here we show that GSKJ4 pharmacologic inhibition of K27 demethylase JMJD3 increases cellular H3K27 methylation in K27M tumor cells and demonstrate potent antitumor activity both in vitro against K27M cells and in vivo against K27M xenografts. Our results demonstrate that increasing H3K27 methylation by inhibiting K27 demethylase is a valid therapeutic strategy for treating K27M-expressing brainstem glioma.

引用

页码：1394 / 1396

页数：3

共 15 条

[1] UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development [J].

Agger, Karl ;

Cloos, Paul A. C. ;

Christensen, Jesper ;

Pasini, Diego ;

Rose, Simon ;

Rappsilber, Juri ;

Issaeva, Irina ;

Canaani, Eli ;

Salcini, Anna Elisabetta ;

Helin, Kristian .

NATURE, 2007, 449 (7163) :731-U10

[2] An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing [J].

Aoki, Yasuyuki ;

Hashizume, Rintaro ;

Ozawa, Tomoko ;

Banerjee, Anu ;

Prados, Michael ;

James, C. David ;

Gupta, Nalin .

JOURNAL OF NEURO-ONCOLOGY, 2012, 108 (01) :29-35

[3] Reduced H3K27me3 and DNA Hypomethylation Are Major Drivers of Gene Expression in K27M Mutant Pediatric High-Grade Gliomas [J].

Bender, Sebastian ;

Tang, Yujie ;

Lindroth, Anders M. ;

Hovestadt, Volker ;

Jones, David T. W. ;

Kool, Marcel ;

Zapatka, Marc ;

Northcott, Paul A. ;

Sturm, Dominik ;

Wang, Wei ;

Radlwimmer, Bernhard ;

Hojfeldt, Jonas W. ;

Truffaux, Nathalene ;

Castel, David ;

Schubert, Simone ;

Ryzhova, Marina ;

Seker-Cin, Huriye ;

Gronych, Jan ;

Johann, Pascal David ;

Stark, Sebastian ;

Meyer, Jochen ;

Milde, Till ;

Schuhmann, Martin ;

Ebinger, Martin ;

Monoranu, Camelia-Maria ;

Ponnuswami, Anitha ;

Chen, Spenser ;

Jones, Chris ;

Witt, Olaf ;

Collins, V. Peter ;

von Deimling, Andreas ;

Jabado, Nada ;

Puget, Stephanie ;

Grill, Jacques ;

Helin, Kristian ;

Korshunov, Andrey ;

Lichter, Peter ;

Monje, Michelle ;

Plass, Christoph ;

Cho, Yoon-Jae ;

Pfister, Stefan M. .

CANCER CELL, 2013, 24 (05) :660-672

[4] Role of histone H3 lysine 27 methylation in polycomb-group silencing [J].

Cao, R ;

Wang, LJ ;

Wang, HB ;

Xia, L ;

Erdjument-Bromage, H ;

Tempst, P ;

Jones, RS ;

Zhang, Y .

SCIENCE, 2002, 298 (5595) :1039-1043

[5] The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression [J].

Chan, Kui-Ming ;

Fang, Dong ;

Gan, Haiyun ;

Hashizume, Rintaro ;

Yu, Chuanhe ;

Schroeder, Mark ;

Gupta, Nalin ;

Mueller, Sabine ;

James, C. David ;

Jenkins, Robert ;

Sarkaria, Jann ;

Zhang, Zhiguo .

GENES & DEVELOPMENT, 2013, 27 (09) :985-990

[6] Brainstem Glioma: A Review [J].

Grimm, Sean A. ;

Chamberlain, Marc C. .

CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, 2013, 13 (05)

[7] Characterization of a diffuse intrinsic pontine glioma cell line: implications for future investigations and treatment [J].

Hashizume, Rintaro ;

Smirnov, Ivan ;

Liu, Sharon ;

Phillips, Joanna J. ;

Hyer, Jeanette ;

McKnight, Tracy R. ;

Wendland, Michael ;

Prados, Michael ;

Banerjee, Anu ;

Nicolaides, Theodore ;

Mueller, Sabine ;

James, Charles D. ;

Gupta, Nalin .

JOURNAL OF NEURO-ONCOLOGY, 2012, 110 (03) :305-313

[8] A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response [J].

Kruidenier, Laurens ;

Chung, Chun-wa ;

Cheng, Zhongjun ;

Liddle, John ;

Che, KaHing ;

Joberty, Gerard ;

Bantscheff, Marcus ;

Bountra, Chas ;

Bridges, Angela ;

Diallo, Hawa ;

Eberhard, Dirk ;

Hutchinson, Sue ;

Jones, Emma ;

Katso, Roy ;

Leveridge, Melanie ;

Mander, Palwinder K. ;

Mosley, Julie ;

Ramirez-Molina, Cesar ;

Rowland, Paul ;

Schofield, Christopher J. ;

Sheppard, Robert J. ;

Smith, Julia E. ;

Swales, Catherine ;

Tanner, Robert ;

Thomas, Pamela ;

Tumber, Anthony ;

Drewes, Gerard ;

Oppermann, Udo ;

Patel, Dinshaw J. ;

Lee, Kevin ;

Wilson, David M. .

NATURE, 2012, 488 (7411) :404-408

[9] Inhibition of PRC2 Activity by a Gain-of-Function H3 Mutation Found in Pediatric Glioblastoma [J].

Lewis, Peter W. ;

Mueller, Manuel M. ;

Koletsky, Matthew S. ;

Cordero, Francisco ;

Lin, Shu ;

Banaszynski, Laura A. ;

Garcia, Benjamin A. ;

Muir, Tom W. ;

Becher, Oren J. ;

Allis, C. David .

SCIENCE, 2013, 340 (6134) :857-861

[10] Polycomb complexes and silencing mechansims [J].

Lund, AH ;

van Lohuizen, M .

CURRENT OPINION IN CELL BIOLOGY, 2004, 16 (03) :239-246

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