Study On Expression Of Wilms' Tumor Gene In Myeloid Leukemias

Wilms' tumor gene (WT1) is a tumor-suppressor gene identified in Wilms' tumor, located on 11p13. The presence of two alternative splices results in four distinct transcripts. Except for kidney, WT1 gene also expresses in other tissues such as normal brain, mesothelial cells, spleen and hematopoietic cells. WT1 protein has both repress and activate transcription functions, it regulates the transcription of some growth factors related to cell growth and differentiation. It was found that WT1 was not a classical tumor-suppressor gene, it possessed some functions as oncogene. Expression of WT1 in leukemias and its relationship with cell growth and apoptosis in myeloid leukemia cell lines have been analysed. WT1 is related to the prognosis of AML and uses as a marker in detecting the minimal residual disease. It is related to proliferation and apoptosis in leukemic cells, but the mechanism is unknown. We studied expression of WT1 gene in AML and CML in different stages, analysed its relation with immunophenotypes and expression of bcl-2 gene. To eluciated its role in leukemogenesis, we studied the effects of WT1 gene expression on cells growth, differentiation and apoptosis in K562 and HL-60 cells.Our results demonstrated that:1.By using RT-PCR method, there are two kinds of WT1 gene products amplified. The positive rate of WT1 gene in de novo AML was 66.0 percent (33/50) for 413bp and 56.0 percent (28/50) for 362bp. WT1 expression became negative or reduced markedly (about one-fifth to one-tenth) after complete remission (CR). WT1 expressed highly in relapsed or refractory patients, but it was negative in long-term survival patients (it may predict the relapse in patients expressing WT1 gene). According to FAB classification, the expression of WT1 gene products in M2, M3 was more intense than that in M4 and M5; it was less frequently expressed in M2a than in M2b. The relationship between expression of WT1 and immunophenoptype...