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

WT1基因在白血病中过表达，并通过其抗凋亡功能参与白血病的发生。在本研究中，蛋白质组学分析显示，在WT1 17AA（+）亚型强制表达的白血病细胞中，一种调节癌细胞代谢的蛋白被去磷酸化。此外，60aa-long wt1衍生肽诱导白血病细胞凋亡。western -western分析表明，这种wt1衍生的肽直接与多种调节癌细胞代谢的蛋白质结合。此外，强制表达WT1 17AA（+）异构体增加了这些蛋白。这些结果表明，WT1 17AA（+）亚型参与了癌细胞代谢，WT1这些功能的分子机制可能成为白血病分子靶向治疗的新靶点。

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.