Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia
Haladyna, Jessica N.
Riedel, Simone S.
Armstrong, Scott A.
Bernt, Kathrin M.
Neff, TobiasNote: Order does not necessarily reflect citation order of authors.
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CitationDanis, E., T. Yamauchi, K. Echanique, X. Zhang, J. N. Haladyna, S. S. Riedel, N. Zhu, et al. 2016. “Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia.” Cell reports 14 (8): 1953-1965. doi:10.1016/j.celrep.2016.01.064. http://dx.doi.org/10.1016/j.celrep.2016.01.064.
AbstractSUMMARY Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Polycomb repressive complex 2 components are frequent in human ETP-ALL, but their functional role is largely undefined. We have studied the involvement of Ezh2 in a murine model of NRASQ61K-driven leukemia that recapitulates phenotypic and transcriptional features of ETP-ALL. Homozygous inactivation of Ezh2 cooperated with oncogenic NRASQ61K to accelerate leukemia onset. Inactivation of Ezh2 accentuated expression of genes highly expressed in human ETP-ALL and in normal murine early thymic progenitors. Moreover, we found that Ezh2 contributes to the silencing of stem-cell- and early-progenitor-cell-associated genes. Loss of Ezh2 also resulted in increased activation of STAT3 by tyrosine 705 phosphorylation. Our data mechanistically link Ezh2 inactivation to stem-cell-associated transcriptional programs and increased growth/survival signaling, features that convey an adverse prognosis in patients.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:26318673
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