Macrophage migration inhibitory factor in the pathogenesis of leukemia (Review)

Abstract

Leukemia is a group of malignant diseases of clonal hematopoietic stem-progenitor cells and its pathological mechanisms remain to be elucidated. Genetic and epigenetic abnormalities, as well as microenvironmental factors, including cytokines, serve critical roles in leukaemogenesis. Macrophage migration inhibitory factor (MIF) has been presented as one of the key regulators in tumorigenesis, angiogenesis and tumor metastasis. This article focuses on the functional role of MIF and its pathway in cancer, particularly in leukemia. MIF/CD74 interaction serves prominent roles in tumor cell survival, such as upregulating BCL-2 and CD84 expression, and activating receptor-type tyrosine phosphatase ζ. Furthermore, MIF upregulation forms a pro-tumor microenvironment in response to hypoxia-induced factors and promotes pro-inflammatory cytokine production. Additionally, polymorphisms of the MIF promoter sequence are associated with leukemia development. MIF signal-targeted early clinical trials show positive results. Overall, these efforts provide a promising means for intervention in leukemia.