干扰素调节因子在慢性粒细胞白血病中的作用

Title:Roles of Interferon Regulatory Factors in Chronic Myeloid Leukemia

Volume: 16 Issue: 7

Author(s): Livia Manzella, Elena Tirrò, Maria Stella Pennisi, Michele Massimino, Stefania Stella, Chiara Romano, Silvia Rita Vitale and Paolo Vigneri

Affiliation:

关键词: IRFs；BCR-ABL；CML；造血；细胞增殖；基因调控。

摘要: 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.

Cite this article as:

Livia Manzella, Elena Tirrò, Maria Stella Pennisi, Michele Massimino, Stefania Stella, Chiara Romano, Silvia Rita Vitale and Paolo Vigneri , Roles of Interferon Regulatory Factors in Chronic Myeloid Leukemia, Current Cancer Drug Targets 2016; 16 (7) . https://dx.doi.org/10.2174/1568009616666160105105857