IRF4 is a suppressor of C-Myc induced B cell leukemia

Simanta Pathak, Shibin Ma, Long Trinh, James Eudy, Kay Uwe Wagner, Shantaram S. Joshi, Runqing Lu

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Interferon regulatory factor 4 (IRF4) is a critical transcriptional regulator in B cell development and function. We have previously shown that IRF4, together with IRF8, orchestrates pre-B cell development by limiting pre-B cell expansion and by promoting pre-B cell differentiation. Here, we report that IRF4 suppresses c-Myc induced leukemia in EμMyc mice. Our results show that c-Myc induced leukemia was greatly accelerated in the IRF4 heterozygous mice (IRF4 +/-Myc); the average age of mortality in the IRF4 +/-Myc mice was only 7 to 8 weeks but was 20 weeks in the control mice. Our results show that IRF4 +/-Myc leukemic cells were derived from large pre-B cells and were hyperproliferative and resistant to apoptosis. Further analysis revealed that the majority of IRF4 +/-Myc leukemic cells inactivated the wild-type IRF4 allele and contained defects in Arf-p53 tumor suppressor pathway. p27 kip is part of the molecular circuitry that controls pre-B cell expansion. Our results show that expression of p27 kip was lost in the IRF4 +/-Myc leukemic cells and reconstitution of IRF4 expression in those cells induced p27 kip and inhibited their expansion. Thus, IRF4 functions as a classical tumor suppressor to inhibit c-Myc induced B cell leukemia in EμMyc mice.

Original languageEnglish (US)
Article numbere22628
JournalPloS one
Volume6
Issue number7
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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