title: Multiple constitutional chromosome translocations of familial nature in Philadelphia chromosome-positive chronic myeloid leukemia: a report on a unique case.
abstract: A case of Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML) featuring 2 additional balanced translocations, t(2;5) and t(6;12), as well as a robertsonian translocation, t(13;14), was diagnosed by routine bone marrow karyotyping. The breakpoints did not involve previously described CML-related chromosomal regions in any of the 3 translocations. Despite the patient's partial response following imatinib therapy, all Ph(-) bone marrow metaphases persistently had the 3 additional chromosomal changes. Moreover, stimulated peripheral B-lymphocytes from the patient also showed the same chromosomal changes, suggesting that we had found a complex constitutional chromosome aberration unrelated to the leukemia. Peripheral blood karyotype analyses of 6 of the 7 closest relatives from 3 generations demonstrated at least 1 of these aberrations, although in different combinations. Standard bone marrow or peripheral blood karyotyping of hematologic disorders may uncover otherwise symptomless, unrelated constitutional changes together with disease-specific chromosome aberrations.A triple constitutional chromosome aberration combined with a hematologic disorder has not been described until now. In addition, multiple constitutional aberrations persisting through at least 3 generations seem to be extremely rare. At present, no direct evidence exists to support a causative relationship between the familial translocations and leukemogenesis.
authors.affiliation: Department of Pathology, 1st Department of Internal Medicine, University of Pécs, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Kajtár
authors.forename: Linda
authors.initials: L
authors.lastname: Deák
authors.forename: Veronika
authors.initials: V
authors.lastname: Kalász
authors.forename: László
authors.initials: L
authors.lastname: Pajor
authors.forename: Lenke
authors.initials: L
authors.lastname: Molnár
authors.forename: Gábor
authors.initials: G
authors.lastname: Méhes
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000473:pathology; D005190:Family; D005260:Female; D006801:Humans; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D008297:Male; D010375:Pedigree; D014178:Translocation, Genetic