| The term WNT is derived from a contraction of the names for the Drosophila melanogaster segment-polarity gene wingless and its mouse orthologue Int1, a mouse proto-oncogene discovered by Nusse and Varmus as an integration site for mouse mammary-tumour viruses. Wnt signaling is initiated by the binding of a Wnt protein to the cysteine-rich domain of a receptor of the frizzled (FZ) family. In the absence of a Wnt signal, β-catenin is phosphorylated by glycogen synthase kinase—3β(GSK-3β), which targets β-catenin for ubiquitinylation and subsequent degradation by proteasomes. However, when Wnt ligands bind to Frizzled receptors, phosphorylation of β-catenin by GSK-3β is inhibited, causing β-catenin stabilization and accumulation, before translocation to the nucleus, where it binds with members of the T-cell factor (TCF) and lymphoid enhancer factor (LEF) transcription factor family, to induce expression of target genes.Signaling through this pathway is involved in various differentiation events during embryonic development and leads to a variety of solid tumor formation when aberrantly activated. Recent studies have implicated a role for Wnt signal transduction at several stages of lymphocyte development and in the self-renewal of haematopoietic stem cells. Several studies from haematological malignancies have provided the evidence that Wnt signaling has a role in malignant haematopoiesis. However, many questions remain to be elucidated in acute leukemia. In order to explore the activation and role of Wnt /β-catenin signaling in acute leukemia, we have completed the following work in this study:...
|
PDF Full Text Request