title: Philadelphia chromosome-positive chronic myelogenous leukemia with deleted fusion of BCR and ABL genes.
abstract: In the great majority of patients with chronic myelogenous leukemia (CML) the reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11), resulting in the Philadelphia (Ph) chromosome produces fusion DNA sequences consisting of the 5' part of the major breakpoint cluster region-1 (M-BCR-1) and the ABL protooncogene which encodes for the P210BCR-ABL phosphoprotein with tyrosine kinase activity implicated in the pathogenesis of CML. Molecular analysis was performed on 25 patients with Ph-positive CML using 2 breakpoint cluster region (bcr) probes within the M-BCR-1 DNA sequences, and two of them did not contain either detectable rearranged DNA homologous to the 5' side bcr probe or ABL-related fusion mRNA. The chromosomal in situ hybridization technique revealed that these two Ph-positive CML cases did not carry DNAs homologous to the 5' bcr or ABL probes on the Ph chromosome. Furthermore, one of the two Ph-positive CML cases did not show either rearranged DNA or regions homologous to the 3' bcr probe on a 9q+ chromosome, while the other CML case showed a rearrangement detected by the 3' bcr probe and transposition of the 3' bcr homologous to the 9q+ chromosome. Thus, the possibility is raised that the BCR/ABL fusion DNA has been deleted in rare CML cases, and that the deletion possibly occurred in a stepwise manner following the formation of the Ph chromosome at any stage of the disease.
authors.affiliation: First Department of Internal Medicine, Tokyo Medical College.
authors.forename: K
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: J H
authors.initials: JH
authors.lastname: Ohyashiki
authors.forename: H
authors.initials: H
authors.lastname: Iwabuchi
authors.forename: T
authors.initials: T
authors.lastname: Tauchi
authors.forename: A
authors.initials: A
authors.lastname: Iwabuchi
authors.forename: K
authors.initials: K
authors.lastname: Toyama
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D015342:DNA Probes; D004262:DNA Restriction Enzymes; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010677:Philadelphia Chromosome; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016315:Proto-Oncogene Proteins c-abl; D051562:Proto-Oncogene Proteins c-bcr; D012689:Sequence Homology, Nucleic Acid
chemical_list: D015342:DNA Probes; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr; D004262:DNA Restriction Enzymes