Antiapoptotic function of WT1 in leukemia and development of WT1-targeting molecular targeted therapy

点击翻译按钮获取中文摘要

The WT1 gene is overexpressed in leukemia and involved in leukemogenesis through its antiapoptotic functions. In the present study, proteomic analysis revealed that a protein which regulates metabolism of cancer cells was dephosphorylated in a leukemia cells with forced expression of WT1 17AA(+) isoform. Moreover, 60aa-long WT1-derived peptide induced apoptosis in leukemia cells. West-western analysis showed that this WT1-derived peptide bound directly to multiple proteins regulating metabolism of cancer cells. Moreover, forced expression of WT1 17AA(+) isoform increased these proteins. These results indicated that WT1 17AA(+) isoform was involved in cancer cell metabolism and the molecular mechanism of these functions of WT1 could be a target of novel molecular targeted therapy for leukemia.