RGD Reference Report - Cooperation between deficiencies of IRF-4 and IRF-8 promotes both myeloid and lymphoid tumorigenesis. - Rat Genome Database

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

Authors: Jo, SH  Schatz, JH  Acquaviva, J  Singh, H  Ren, R 
Citation: Jo SH, etal., Blood. 2010 Oct 14;116(15):2759-67. doi: 10.1182/blood-2009-07-234559. Epub 2010 Jun 28.
RGD ID: 11530030
Pubmed: PMID:20585039   (View Abstract at PubMed)
PMCID: PMC2974585   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2009-07-234559   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Irf4  (interferon regulatory factor 4)
Irf8  (interferon regulatory factor 8)

Genes (Mus musculus)
Irf4  (interferon regulatory factor 4)
Irf8  (interferon regulatory factor 8)

Genes (Homo sapiens)
IRF4  (interferon regulatory factor 4)
IRF8  (interferon regulatory factor 8)


Additional Information