Alterations in WNT Signaling in Leukemias

Abstract

The WNT/β–catenin signaling pathway plays an important role in the differentiation and proliferation of hematopoietic cells. In recent years, special attention has been paid to the role of impairments in the WNT signaling path–way in pathogenesis of malignant neoplasms of the hematopoietic system. Disorders in the WNT/β–catenin signaling in leukemias identified to date include hypersensitivity to the WNT ligands, epigenetic repression of WNT antagonists, over–expression of WNT ligands, impaired β–catenin degradation in the cytoplasm, and changes in the activity of the TCF/Lef transcription factors. At the molecular level, these impairments involve overexpression of the FZD protein, hypermethylation of the SFRP, DKK, WiF, Sox, and CXXC gene promoters, overexpression of Lef1 and plakoglobin, mutations in GSK3β, and β–catenin phosphorylation by the BCR–ABL kinase. This review is devoted to the systematization of these data.