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Detection of fusion transcripts generated by the inversion 16 chromosome in
acute myelogenous leukemia
DF Claxton, P Liu, HB Hsu, P Marlton, J Hester, F Collins, AB Deisseroth, JD Rowley and MJ Siciliano
Department of Hematology, University of Texas M.D. Anderson Cancer Center,
Houston 77030.
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.
Volume 83,
Issue 7,
pp. 1750-1756,
04/01/1994
Copyright © 1994 by The American Society of Hematology
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