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

Research output: Contribution to journalArticle

207 Citations (Scopus)

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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Pediatrics
Methylation
Glioma
Histones
Brain Stem
Ports and harbors
Heterografts
Tumors
Cells
Mutation
Therapeutics
Neoplasms
In Vitro Techniques

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hashizume, R., Andor, N., Ihara, Y., Lerner, R., Gan, H., Chen, X., ... 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

Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. / Hashizume, Rintaro; Andor, Noemi; Ihara, Yuichiro; Lerner, Robin; Gan, Haiyun; Chen, Xiaoyue; Fang, Dong; Huang, Xi; Tom, Maxwell W.; Ngo, Vy; Solomon, David; Mueller, Sabine; Paris, Pamela L.; Zhang, Zhiguo; Petritsch, Claudia; Gupta, Nalin; Waldman, Todd A.; James, C. David.

In: Nature Medicine, Vol. 20, No. 12, 01.12.2014, p. 1394-1396.

Research output: Contribution to journalArticle

Hashizume, R, Andor, N, Ihara, Y, Lerner, R, Gan, H, Chen, X, Fang, D, Huang, X, Tom, MW, Ngo, V, Solomon, D, Mueller, S, Paris, PL, Zhang, Z, Petritsch, C, Gupta, N, Waldman, TA & James, CD 2014, 'Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma', Nature Medicine, vol. 20, no. 12, pp. 1394-1396. https://doi.org/10.1038/nm.3716
Hashizume R, Andor N, Ihara Y, Lerner R, Gan H, Chen X et al. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nature Medicine. 2014 Dec 1;20(12):1394-1396. https://doi.org/10.1038/nm.3716
Hashizume, Rintaro ; Andor, Noemi ; Ihara, Yuichiro ; Lerner, Robin ; Gan, Haiyun ; Chen, Xiaoyue ; Fang, Dong ; Huang, Xi ; Tom, Maxwell W. ; Ngo, Vy ; Solomon, David ; Mueller, Sabine ; Paris, Pamela L. ; Zhang, Zhiguo ; Petritsch, Claudia ; Gupta, Nalin ; Waldman, Todd A. ; James, C. David. / Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. In: Nature Medicine. 2014 ; Vol. 20, No. 12. pp. 1394-1396.
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