RT-PCR DIAGNOSIS OF PATIENTS WITH ACUTE NONLYMPHOCYTIC LEUKEMIA AND INV(16)(P13Q22) AND IDENTIFICATION OF NEW ALTERNATIVE SPLICING IN CBFB-MYH11 TRANSCRIPTS

As acute nonlymphocytic leukemia (ANLL) with inv(16) (p13q22) or t(16; 16)(p13; q22) has been shown to result from the fusion of transcripti on factor subunit core binding factor (CBFB) to a myosin heavy chain ( MYH11), we sought to design methods to detect this rearrangement using reverse transcriptase-polymerase chain reaction (RT-PCR). In all of 2 7 inv(16)(p13q22) and four t(16;16)(p13;q22) cases tested, a chimeric CBFB-MYH11 transcript coding for an in-frame fusion protein was detect ed. In a more extensive RT-PCR analysis with different primer pairs, w e detected a second new chimeric CBFB-MYH11 transcript in 10 of 11 pat ients tested. The CBFB-MYH11 reading frame of the second transcript wa s maintained in one patient but not in the others. We show that the di fferent CBFB-MYH11 transcripts in one patient arise from alternative s plicing. Translation of the transcript in which the CBFB-MYH11 reading frame is not maintained leads to a slightly truncated CBFB protein. ( C) 1995 by The American Society of Hematology.