The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34.
The specific (6;9)(p23;q34) chromosomal translocation is associated with a defined subtype of acute nonlymphocytic leukemia (ANLL). The 9q34 breakpoint is located at the telomeric side of the c-abl gene. Through a combination of chromosome jumping, long-range mapping, and chromosome walking, the chromosome 9 breakpoints of several t(6;9) ANLL patients were localized within a defined region of 8 kilobases (kb), 360 kb telomeric of c-abl. Subsequent cDNA cloning revealed that this region represented an intron in the middle of a gene, called Cain (can), encoding a 7.5-kb transcript. Disruption of the can gene by the translocation resulted in the expression of a new 5.5-kb can mRNA from the 6p- chromosome. Isolation of chromosome 6 sequences showed that breakpoints on 6p23 also clustered within a limited stretch of DNA. These data strongly suggest a direct involvement of the translocation in the leukemic process of t(6;9) ANLL.
von Lindern
M
M
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Poustka
A
A
Lerach
H
H
Grosveld
G
G
D015139:Blotting, Southern; D002460:Cell Line; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular; D003360:Cosmids; D004273:DNA, Neoplasm / Q000235:genetics; D015723:Gene Library; D006801:Humans; D007438:Introns; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D013737:Testis / Q000378:metabolism; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm