title: BCR/ABL rearrangement in two cases of Philadelphia chromosome negative chronic myeloid leukemia: deletion on the derivative chromosome 9 may or not be present.
abstract: The BCR/ABL gene rearrangement is the causing factor in chronic myeloid leukemia (CML). In most cases, it is cytogenetically visualized as a translocation between chromosomes 9 and 22, known as the Philadelphia (Ph) translocation. About 5-10% of CML patients lack cytogenetic evidence of the Ph translocation but show BCR/ABL fusion by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction. Deletions around the breakpoints on the derivative 9 including ABL and or BCR sequences occur in 10-15% of Ph+ CML patients and are thought to have prognostic significance. We describe two patients with CML and normal karyotype in whom cryptic rearrangements involving chromosomes 9 and 22 resulted in the causative BCR/ABL gene. FISH with a three-color probe combination revealed BCR/ABL fusion on chromosome 9 without deletion in one patient; the other patient had BCR/ABL on chromosome 22 with an associated derivative 9 deletion. We discuss the proposed mechanisms in the formation of BCR/ABL in the setting of a normal karyotype. Some authors reported that patients with the chimeric gene located on the derivative 9 have a poor clinical course. We suggest that deletion rather than location of the chimeric gene alone is more likely to be associated with prognosis.
authors.affiliation: Department of Pathology, Division of Molecular Pathology, Johns Hopkins University, 600 North Wolfe Street, Park SB 202, Baltimore, MD 21287, USA. dbatist1@jhmi.edu
authors.forename: Denise A S
authors.initials: DA
authors.lastname: Batista
authors.forename: Anita
authors.initials: A
authors.lastname: Hawkins
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Constance A
authors.initials: CA
authors.lastname: Griffin
mesh_terms: D000328:Adult; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000235:genetics*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D016044:Fusion Proteins, bcr-abl