Alternative, out-of-frame runt/MTG8 transcripts are encoded by the derivative (8) chromosome in the t(8;21) of acute myeloid leukemia M2.
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.
Tighe
J E
JE
Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Calabi
F
F
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D029721:Drosophila Proteins; D005091:Exons; D015870:Gene Expression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein; D015183:Restriction Mapping; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D014157:Transcription Factors; C080833:run protein, Drosophila