Cooperation between deficiencies of IRF-4 and IRF-8 promotes both myeloid and lymphoid tumorigenesis

Seung Hee Jo, Jonathan H Schatz, Jaime Acquaviva, Harinder Singh, Ruibao Ren

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Interferon regulatory factor 4 (IRF-4) plays important functions in B- and T-cell development and immune response regulation and was originally identified as the product of a proto-oncogene involved in chromosomal translocations in multiple myeloma. Although IRF-4 is expressed in myeloid cells, its function in that lineage is not known. The closely related family member IRF-8 is a critical regulator of myelopoiesis, which when deleted in mice results in a syndrome highly similar to human chronic myelogenous leukemia. In early lymphoid development, we have shown previously that IRF-4 and IRF-8 can function redundantly. We therefore investigated the effects of a combined loss of IRF-4 and IRF-8 on hematologic tumorigenesis. We found that mice deficient in both IRF-4 and IRF-8 develop from a very early age a more aggressive chronic myelogenous leukemia-like disease than mice deficient in IRF-8 alone, correlating with a greater expansion of granulocyte-monocyte progenitors. Although these results demonstrate, for the first time, that IRF-4 can function as tumor suppressor in myeloid cells, interestingly, all mice deficient in both IRF-4 and IRF-8 eventually develop and die of a B-lymphoblastic leukemia/lymphoma. Combined losses of IRF-4 and IRF-8 therefore can cooperate in the development of both myeloid and lymphoid tumors.

Original languageEnglish (US)
Pages (from-to)2759-2767
Number of pages9
JournalBlood
Volume116
Issue number15
DOIs
StatePublished - Oct 14 2010
Externally publishedYes

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Carcinogenesis
Myeloid Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Tumors
Myelopoiesis
Granulocyte Precursor Cells
Genetic Translocation
T-cells
Proto-Oncogenes
interferon regulatory factor-4
interferon regulatory factor-8
Multiple Myeloma
Monocytes
Neoplasms
T-Lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

Cite this

Cooperation between deficiencies of IRF-4 and IRF-8 promotes both myeloid and lymphoid tumorigenesis. / Jo, Seung Hee; Schatz, Jonathan H; Acquaviva, Jaime; Singh, Harinder; Ren, Ruibao.

In: Blood, Vol. 116, No. 15, 14.10.2010, p. 2759-2767.

Research output: Contribution to journalArticle

Jo, Seung Hee ; Schatz, Jonathan H ; Acquaviva, Jaime ; Singh, Harinder ; Ren, Ruibao. / Cooperation between deficiencies of IRF-4 and IRF-8 promotes both myeloid and lymphoid tumorigenesis. In: Blood. 2010 ; Vol. 116, No. 15. pp. 2759-2767.
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