Role of the Wilms' tumor gene WT1 in human leukemogenesis

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1. The wild-type WT1 gene is expressed in almost all leukemias and thus WT1mRNA is a pan-leukemia tumor marker.2. The growth of leukemia cells was inhabited by the treatment with WT1 antisense oligomers.3. Constitutive expression of the wild-type WT1 gene inhibited differentiation of 32D c13 myeloid progenitor cells and instead induced proliferation of the cells in response to G-CSF.4. Normal myeloid progenitor cells transfected with the wild-type WT1 cDNA-integrated retroviral vetcor formed more CFU-G, CFU-M, and CFU-GM colonies compared to those transfected with control vector in response to G-CSF.5. To determine the frequencies of WT1-expressing bone marrow cells, 1,632 CD34^+ human bone marrow progenitor cells were examined for the WT1 expression by using single-cell RT-PCR. Only 19 (1.2%) of the 1,632 CD34^+ cells expressed WT1mRMA and the WT1mRMA expression levels were similar between normal CD34^+ and leukemia single cells, suggesting that WT1-expressing CD34^+ cells were normal counterparts of WT1-expressing leukemia cells.