Mechanisms of genesis of variant translocation in chronic myeloid leukemia are not correlated with ABL1 or BCR deletion status or response to imatinib therapy.
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.
Richebourg
Steven
S
Laboratory of Medical Genetics, Hospital Jeanne de Flandre, University Hospital Regional Center-CHRU, Avenue Eugène Avinée, 59037 Lille cedex, France.
Eclache
Virginie
V
Perot
Christine
C
Portnoi
Marie-France
MF
Van den Akker
Jacqueline
J
Terré
Christine
C
Maareck
Odile
O
Soenen
Valérie
V
Viguié
Franck
F
Laï
Jean-Luc
JL
Andrieux
Joris
J
Corm
Sélim
S
Roche-Lestienne
Catherine
C
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
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