title: Double minutes containing amplified bcr-abl fusion gene in a case of chronic myeloid leukemia treated by imatinib.
abstract: Amplification of the bcr-abl fusion gene has recently been associated with resistance to imatinib therapy in chronic myeloid leukemia (CML). A 55-yr-old man was diagnosed with Philadelphia (Ph) chromosome-positive CML. Resistance to interferon treatment and occurrence of blastic phase lead to the decision of imatinib therapy. After two autologous stem cell transplantation, the patient reverted to chronic phase with a decrease in the proportion of Ph chromosome-positive cells under imatinib. A second blastic phase occurred 4 months after transplantation, of which the patient died. Cytogenetic studies, including fluorescent in situ hybridization, showed a (9;22)(q34;q11) translocation and one bcr-abl fusion gene during the whole evolution, but for the last 2 months. Bcr-abl gene amplification (over 25 copies) was noted while banding cytogenetics showed a karyotype of 55-62 chromosomes with multiple double minutes (dmin). To the best of our knowledge, dmin containing amplified bcr-abl gene has never been reported in patients with CML. Therefore, although we cannot exclude that the gene amplification was strictly associated with disease progression, our data may suggest that the amplification resulted in resistance to imatinib.
authors.affiliation: Faculté de Médecine, Université de Bretagne Occidentale, Brest.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Morel
authors.forename: Marie-Josée Le
authors.initials: MJ
authors.lastname: Bris
authors.forename: Angèle
authors.initials: A
authors.lastname: Herry
authors.forename: Geneviève Le
authors.initials: GL
authors.lastname: Calvez
authors.forename: Véronique
authors.initials: V
authors.lastname: Marion
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Abgrall
authors.forename: Christian
authors.initials: C
authors.lastname: Berthou
authors.forename: Marc De
authors.initials: MD
authors.lastname: Braekeleer
mesh_terms: D000782:Aneuploidy; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides; D001752:Blast Crisis / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D020223:Chromosome Painting; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D017809:Fatal Outcome; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D036102:Peripheral Blood Stem Cell Transplantation; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D014182:Transplantation, Autologous
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D009363:Neoplasm Proteins; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D006918:Hydroxyurea