The Interferon Regulatory Factor (IRF) family consists of multiple
transcription factors involved in the regulation of a variety of biological processes.
Originally identified as transcriptional regulators of the type I interferon system,
IRFs play a pivotal role in adaptive immunity, cell growth, differentiation and
tumorigenesis. Hence, understanding IRF biology has important implications in
the host response to cancer development and progression. Many lines of evidence
suggest that different IRFs are involved in the pathogenesis of Chronic Myeloid
Leukemia (CML), a myeloproliferative disorder caused by the BCR-ABL
oncoprotein. BCR-ABL displays constitutive tyrosine kinase activity that favors cell
proliferation, inhibits apoptosis and allows cell survival even in the absence of
proper adhesion to the extracellular matrix. Different BCR-ABL tyrosine kinase inhibitors are currently
available for CML treatment. These drugs are able to generate eight year CML-specific overall survival
rates >90%, only a minority of patients will achieve molecular responses compatible with drug
discontinuation. Thus, there is an unmet need for additional therapeutic targets that may lead to the cure
of most patients diagnosed with CML. A growing body of evidence has suggested a role for both IRF4
and IRF8 in the pathogenesis of CML. Furthermore, IRF1 is consistently deleted at one or both alleles in
patients with leukemia and myelodysplasia. Finally, we have recently demonstrated that IRF5 is a target
of BCR-ABL kinase activity and reduces CML cell proliferation. In this article, we provide an update on
the current knowledge of the role of the IRFs in CML.
Keywords: IRFs, BCR-ABL, CML, hematopoiesis, proliferation, gene-regulation.
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