The role of the tumor suppressor gene WT1 in human leukemogenesis.

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1. The wild-type WT1 gene was expressed in not only leukemia but also solid tumors, including lung cancers. The growth of these cancer cells was inhibited by the treatment with WT1 antisense oligomers.2. Leukemic cell line K562 was arrested at G_2/M checkpoint by the treatment with WT1 antisense oligomers.3. We have established the method to measure individually four different splicing variants (17AA+/KTS+, 17AA+/KTS-, 17AA-/KTS+, 17AA-/KTS-). By using this method, it was found that a 17AA+/KTS+ transcript was major in leukemic cells.4. When the wild-type WT1 gene was transfected into myeloid progenitor cell 32D and the gene was constitutively expressed, the apoptosis of the 32D cells was inhibited.5. A novel WT1-binding protein was cloned and named as WTIP was localized in splicesome and so considered as a splicing factor.