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. (C) 1996 by The American Society of Hematology.