title: Absence in Ph-negative, M-BCR rearrangement-positive chronic myelogenous leukemia of linkage between 5' ABL and 3' M-BCR sequences in Philadelphia translocation.
abstract: The Philadelphia (Ph) chromosome can be detected in the vast majority of patients with chronic myelogenous leukemia (CML). We performed a long-range analysis of chromosomal translocation junction by pulsed-field gel electrophoresis (PFGE) techniques, to examine whether molecular evidence of a reciprocal Ph translocation exists in Ph-positive CML as well as Ph-negative, M-BCR rearrangement-positive CML. The rearrangement within M-BCR and ABL was detected in all patients including nine Ph-positive CML, and three Ph-negative CML. The rearranged 3'-abl fragments showed comigration with rearranged 5'-bcr fragment in rare-cutting restriction enzyme digests in all patients with Ph-positive CML. Thus, the physical linkage of the 3' part of ABL to the 5' side of M-BCR on 22q-chromosome was shown. The same linkage was also demonstrated in all three patients with Ph-negative CML. Meanwhile, the rearranged 3'-bcr fragments showed comigration with rearranged pHabl5' (or T39-1-2) fragments in all patients with Ph-positive CML, indicating the linkage of the 5' end of ABL to the 3' part of M-BCR on 9q+ chromosome. However, this linkage was absent in two Ph-negative CML patients who could be studied. The results suggest that a genomic insertion of 3' ABL into M-BCR in Ph-negative CML occurs by a single cytogenetic event rather than a two-translocation mechanism.
authors.affiliation: Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishigaki
authors.forename: S
authors.initials: S
authors.lastname: Misawa
authors.forename: J
authors.initials: J
authors.lastname: Inazawa
authors.forename: T
authors.initials: T
authors.lastname: Abe
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015321:Gene Rearrangement; D016313:Genes, abl; D008040:Genetic Linkage; D006801:Humans; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D015183:Restriction Mapping; D014178:Translocation, Genetic