Mutations in the Wilms' tumor gene WT1 in leukemias

The tissue-specific Wilms' tumor gene WT1 is expressed in a range of acute leukemias and hematopoietic cell lines. Using single-strand conformational polymorphism analysis, we have found mutations in the WT1 gene in 4 of 36 acute leukemias. WT1 mutations are found in 15% of cases of acute myeloid leukemia, in which they are associated with a poor response to chemotherapy. The mutations comprise small insertions in exons 1 and 7 and a nonsense mutation in exon 9. All are predicted to produce a truncated WT1 protein with absence or disruption of the zinc finger region. These are the first mutations in the WT1 gene to be described in sporadic leukemia.