WT1
小结
WT1编码一种转录因子，其在整个发育过程中以组织特异性方式表达，参与细胞发育和细胞存活。WT1与TP53蛋白的稳定有关，调节了多种靶基因的表达，其中包括MYC和BCL2，它们对细胞生长和代谢很重要。在造血细胞中，WT1与表观遗传蛋白TET2和TET3相互作用调节DNA的羟甲基化。WT1最初在Wilms肿瘤中被发现是一种肿瘤抑制因子，但WT1的丢失只导致了一部分肾母细胞瘤的发病机制。在急性髓细胞白血病（AML）患者中发现WT1的体细胞突变，并预测其功能丧失并导致DNA结合活性降低。另外，TET和IDH家族突变在AML患者中与WT1突变不会同时发生，表明WT1作为DNA甲基化调控因子而发挥作用。WT1在大多数的髓系和淋巴样白血病患者中呈现过表达。
WT1 (Wilms tumor 1 gene) is a transcription factor expressed in a tissue-specific manner throughout development . WT1 has been implicated in the protein stabilization of TP53 and regulates the expression of several target genes include MYC and BCL2, which are important for cellular growth and metabolism. In hematopoietic cells, WT1 interacts with the epigenetic proteins TET2 and TET3 that regulate hydroxymethylation of DNA, an epigenetic modification of DNA that may also serve as a methylation state intermediate. Loss of WT1 expression results in depletion of global 5-hydroxymethylation levels, implicating WT1 in the regulation of DNA methylation. WT1 was initially discovered as a tumor suppressor in Wilms’ tumor ; however, WT1 loss only contributes to the pathogenesis of a fraction of Wilms' tumors. Somatic WT1 mutations hav been identified in patients with acute myeloid leukemia (AML) and are predicted to be loss-of-function, leading to decreased DNA binding activity. Importantly, TET and IDH family mutations are mutually exclusive with WT1 mutations in AML patients, suggesting that WT1 functions as a regulator of DNA methylation. Patients with WT1 mutations may be increasingly sensitive to hypomethylating agents, such as azacytidine, due to the role of WT1 in the regulation of methylation. WT1 is overexpressed in a large percentage of patients with myeloid and lymphoid leukemias. Vaccines that target overexpression of WT1 are currently in clinical development.