Search

The t(8;21)(q22;q22) is consistently associated with acute myeloid leukemia (AML) M2. Recent data have suggested that breakpoints on chromosome 21 are clustered within a single intron of a novel gene, AML 1,just downstream of a region of homology to the runtgene of D melanogaster.In this report, we confirm rearrangement at the same location in at least 12 of 18 patients with t(8;21). Furthermore, we have isolated recombinant clones spanning the breakpoint regions on both the der(8) and the der(21) from one patient. By using α chromosome 8 probe derived from these clones, we show that t(8;21) breakpoints are also clustered on chromosome 8.

In the t(8;21) of acute myeloid leukemia (AMD M2, breakpoints are clustered on both chromosomes. The chromosome 21 breakpoint cluster region (bcr) falls within the runtlocus, 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 MTG8locus. Unexpectedly, not only does the bcr map upstream of the most 5‘ MTG8exon 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.