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Alternative, out-of-frame runt/MTG8 transcripts are encoded by the
derivative (8) chromosome in the t(8;21) of acute myeloid leukemia M2
JE Tighe and F Calabi
Department of Haematology, Royal Postgraduate Medical School, Hammersmith
Hospital, London, UK.
In the t(8;21) of acute myeloid leukemia (AML) M2, breakpoints are
clustered on both chromosomes. The chromosome 21 breakpoint cluster region
(bcr) falls within the runt locus, in the intron immediately downstream of
the exons encoding an evolutionary conserved domain (the runt box).
Transcripts in which the runt box is fused in frame to a novel sequence
derived from chromosome 8 (MTG8) have been previously identified and have
been assumed to constitute a critical leukemogenic event. Here we show
physical linkage of the chromosome 8 bcr to the MTG8 locus. Unexpectedly,
not only does the bcr map upstream of the most 5' MTG8 exon found in
runt/MTG8 fusion transcripts, but it also maps upstream of a further 5'
exon. In addition, we demonstrate the presence of alternative transcripts,
originating from the der(8) chromosome, in which runt is out of frame with
MTG8. Thus, runt truncation per se, rather than its fusion to MTG8, may be
the crucial leukemogenic event.
Volume 84,
Issue 7,
pp. 2115-2121,
10/01/1994
Copyright © 1994 by The American Society of Hematology
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