Detection of fusion transcripts generated by the inversion 16 chromosome in acute myelogenous leukemia

Pericentric inversion of chromosome 16 inv(16)(p13q22) and the related t(16;16)(p13;q22) are seen in a subset of acute myelogenous leukemia (AML) phenotypically and prognostically differing from other cases. We have recently shown that inv(16) results in fusion of CBFB/PEBP2B, a gene encoded at 16q22 to MYH11, a smooth muscle myosin heavy chain gene encoded at 16p13. Chimeric transcripts consisting of upstream CBFB fused to downstream MYH11 coding sequences result from this fusion. In this study we have examined a series of 37 of these cases using reverse transcriptase-polymerase chain reaction (RT-PCR) to detect expression of a hybrid CBFB/MYH11 transcript. Chimeric cDNAs were detected in all but 1 of 37 leukemias with typical inv(16) or t(16;16). Such chimeric products were not seen in a case with inv(16)(p13q24) (ie, a variant q arm breakpoint) or any of 10 cases of AML without these chromosomal changes. Four different chimeric transcripts were found, representing differing fusion points within MYH11 spliced to position 495 of CBFB. Primer sets are described for efficient amplification of these different cDNA forms. Amplification of cDNA showed that all but 17 codons of the CBFB coding sequence are included in the abnormal transcripts. RT-PCR was shown to be highly sensitive and potentially useful for detection of leukemic cells during morphologic remission.