title: Deletions adjacent to BCR and ABL1 breakpoints occur in a substantial minority of chronic myeloid leukemia patients with masked Philadelphia rearrangements.
abstract: Deletions at the t(9;22) breakpoint regions, found in 15% of chronic myeloid leukemia patients (CML) with an overt Philadelphia (Ph) translocation, are associated with an adverse disease prognosis in patients receiving interferon-alpha therapy. The incidence of deletions has been shown to vary for different cytogenetic subgroups of CML, with a significantly higher incidence of deletion in patients with a variant Ph translocation. To date, however, the frequency of such deletions in the subgroup of CML patients in whom the BCR/ABL1 fusion arises via submicroscopic chromosomal insertion (masked Ph) has not been investigated. We report the evaluation of 14 patients with masked Ph-positive CML for the presence of deletions extending 3' from BCR and 5' from ABL1 using two triple-color BCR/ABL probes. Deletions were identified in 3 patients (21%), encompassing sequences 5' to ABL1 in two of these and sequences 3' to BCR in the remaining patient, thus demonstrating that the phenomenon is a significant feature of the masked Ph CML subgroup. Furthermore, our findings are consistent with the notion that loss of genomic material is a potential side effect of any DNA breakage event at the 9q34.1 and 22q11.2 chromosomal regions, regardless of the subsequent mechanism of chromosomal rearrangement.
authors.affiliation: Department of Haematology, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Valeria A S
authors.initials: VA
authors.lastname: De Melo
authors.forename: Dragana
authors.initials: D
authors.lastname: Milojkovic
authors.forename: David
authors.initials: D
authors.lastname: Marin
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: Elisabeth P
authors.initials: EP
authors.lastname: Nacheva
authors.forename: Alistair G
authors.initials: AG
authors.lastname: Reid
mesh_terms: D019457:Chromosome Breakage; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D020732:Cytogenetic Analysis; D017353:Gene Deletion; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D016315:Proto-Oncogene Proteins c-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr