Aberrant mRNA splicing has been observed frequently in solid tumors and shown to play a functionally significant role in tumorgenesis. Here we demonstrate that the DEAH-Box splicing factor gene, Prp16, is amplified in fresh human acute myeloid leukemia (AML) and in established AML cell lines. Prp16, an RNA-dependent ATPase required for pre-mRNA splicing, maps to chromosome 16q22, a region frequently altered in AML. Amplification of the Prp16 gene was initially detected using digital karyotyping, a powerful technique for analyzing genome-wide alterations in DNA copy number and verified by quantitative real-time PCR. Analysis of mRNA expression profiles revealed that Prp16 transcripts were present at high levels in 22 of 39 cases of AML (56%) and in both AML cell lines examined. There was a strong correlation between gene amplification and mRNA expression levels. To our knowledge, this is the first demonstration linking aberrant expression of a splicing enzyme to leukemogenesis. The classification and clinical outcome of the AML cases is being correlated with the presence or absence of Prp16 amplification. The identification of leukemia-specific splicing event(s) may provide a novel target for therapeutic intervention.

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