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

Rintaro Hashizume*, Noemi Andor, Yuichiro Ihara, Robin Lerner, Haiyun Gan, Xiaoyue Chen, Dong Fang, Xi Huang, Maxwell W. Tom, Vy Ngo, David Solomon, Sabine Mueller, Pamela L. Paris, Zhiguo Zhang, Claudia Petritsch, Nalin Gupta, Todd A. Waldman, C. David James

*Corresponding author for this work

Research output: Contribution to journalArticle

215 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1394-1396
Number of pages3
JournalNature Medicine
Volume20
Issue number12
DOIs
StatePublished - Dec 1 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hashizume, R., Andor, N., Ihara, Y., Lerner, R., Gan, H., Chen, X., Fang, D., Huang, X., Tom, M. W., Ngo, V., Solomon, D., Mueller, S., Paris, P. L., Zhang, Z., Petritsch, C., Gupta, N., Waldman, T. A., & James, C. D. (2014). Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nature Medicine, 20(12), 1394-1396. https://doi.org/10.1038/nm.3716