title: Cytogenetic, fluorescence in situ hybridization, and genomic array characterization of chronic myeloid leukemia with cryptic BCR-ABL1 fusions.
abstract: Chronic myeloid leukemia (CML) is characterized by the breakpoint cluster region (BCR)-Abelson murine leukemia (ABL1) fusion gene. In approximately 1% of CML cases, the Philadelphia chromosome associated with the BCR-ABL1 fusion gene is not present, and the BCR-ABL1 fusion gene is generated by cryptic insertion or sequential translocations. In this study, we describe the cytogenetic and molecular features of five CML patients with cryptic BCR-ABL1 fusion genes using karyotype, fluorescence in situ hybridization (FISH), and whole genome single nucleotide polymorphism array techniques. Two cases of CML in the chronic phase (CP) had a normal karyotype, and three cases of CML in the blast phase (BP) had an abnormal karyotype with neither a typical nor variant t(9;22). By BCR-ABL1 metaphase FISH analysis, we found that fusion signals were localized on chromosomes 9 (3 cases), 22 (1 case), and both 9 and 22 (1 case). In two cases of CML-BP, duplication of the BCR-ABL1 fusion gene occurred as a result of mitotic recombination between homologous chromosomes. Copy number losses involving the IKZF1 gene were observed in two patients with CML-BP. This study demonstrates for the first time the acquisition of additional BCR-ABL1 fusion genes through mitotic recombination in CML with cryptic BCR-ABL1.
authors.affiliation: Clinical Cytogenetics Laboratory, Department of Pathology, University of Michigan, Ann Arbor, MI, USA. Electronic address: linashao@med.umich.edu.
authors.forename: Lina
authors.initials: L
authors.lastname: Shao
authors.affiliation: Clinical Cytogenetics Laboratory, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Sue
authors.initials: S
authors.lastname: Miller
authors.affiliation: Clinical Cytogenetics Laboratory, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keller-Ramey
authors.affiliation: Clinical Cytogenetics Laboratory, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Clinical Cytogenetics Laboratory, Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Roulston
mesh_terms: D001752:Blast Crisis / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D020732:Cytogenetic Analysis; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D059785:Karyotype; D015466:Leukemia, Myeloid, Chronic-Phase / Q000235:genetics*; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr
keywords: Chronic myeloid leukemia; cryptic BCR-ABL1; single nucleotide polymorphism array