Stat3 promotes the development of erythroleukemia by inducing Pu.1 expression and inhibiting erythroid differentiation

S. Hegde, S. Ni, S. He, D. Yoon, G. S. Feng, S. S. Watowich, R. F. Paulson, P. A. Hankey

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Leukemogenesis requires two classes of mutations, one that promotes proliferation and one that blocks differentiation. The erythroleukemia induced by Friend virus is a multistage disease characterized by an early proliferative stage driven by the interaction of the viral glycoprotein, gp55, with Sf-Stk and the EpoR, and a late block to differentiation resulting from retroviral insertion in the Pu.1 locus. We demonstrate here that activation of Stat3 by Sf-Stk in the early stage of disease is essential for the progression of erythroleukemia in the presence of differentiation signals induced by the EpoR, but is dispensable in the late stages of the disease. Furthermore, we identify Pu.1 as a Stat3 target gene in the early stages of erythroleukemia development. Our results support a model whereby the activation of Stat3 in the early stage of disease plays a pivotal role in regulating differentiation through the upregulation of Pu.1, thus inhibiting differentiation and favoring the expansion of infected erythroblasts and enhancing the pool of progenitors available for the acquisition of additional mutations, including insertional activation of Pu.1, resulting in full leukemic transformation.

Original languageEnglish (US)
Pages (from-to)3349-3359
Number of pages11
JournalOncogene
Volume28
Issue number38
DOIs
StatePublished - Sep 24 2009

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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