title: Mechanisms of genesis of variant translocation in chronic myeloid leukemia are not correlated with ABL1 or BCR deletion status or response to imatinib therapy.
abstract: Many published studies have indicated that various mechanisms could be involved in the genesis of variant chronic myelogeneous leukemia (CML) translocations. These are mainly one-step or two-step mechanisms, associated or not with deletions adjacent to the translocation junction on der(9) or der(22) chromosomes (or both). Based on the mechanism of genesis, it has been suggested that the complexity may affect the occurrence of ABL1 and BCR deletions (either or both), or may be associated with the CML disease course, and thus could determine the response to imatinib therapy. Through a retrospective molecular cytogenetic study of 41 CML patients with variant Philadelphia chromosome (Ph), we explored the genesis of these variant rearrangements and analyzed the correlation with deletion status and imatinib efficiency. Our results confirmed that the one-step mechanism is the most frequent, evidenced in 30 of 41 patients (73%); 3 patients demonstrated other more complex multistep events and 8 patients (19.5%) harbored ABL1 or BCR deletions that are not significantly associated with the complexity of translocation genesis. We also found no association between one-step, two-step, or multistep mechanisms and the response to imatinib therapy.
authors.affiliation: Laboratory of Medical Genetics, Hospital Jeanne de Flandre, University Hospital Regional Center-CHRU, Avenue Eugène Avinée, 59037 Lille cedex, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Richebourg
authors.forename: Virginie
authors.initials: V
authors.lastname: Eclache
authors.forename: Christine
authors.initials: C
authors.lastname: Perot
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Portnoi
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Van den Akker
authors.forename: Christine
authors.initials: C
authors.lastname: Terré
authors.forename: Odile
authors.initials: O
authors.lastname: Maareck
authors.forename: Valérie
authors.initials: V
authors.lastname: Soenen
authors.forename: Franck
authors.initials: F
authors.lastname: Viguié
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Laï
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.forename: Sélim
authors.initials: S
authors.lastname: Corm
authors.forename: Catherine
authors.initials: C
authors.lastname: Roche-Lestienne
mesh_terms: D001549:Benzamides; D020732:Cytogenetic Analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate; D014178:Translocation, Genetic
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr