Double minutes containing amplified bcr-abl fusion gene in a case of chronic myeloid leukemia treated by imatinib

Eur J Haematol. 2003 Apr;70(4):235-9. doi: 10.1034/j.1600-0609.2003.00046.x.

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.

Publication types

  • Case Reports

MeSH terms

  • Aneuploidy
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Benzamides
  • Blast Crisis / genetics*
  • Blast Crisis / pathology
  • Chromosome Aberrations
  • Chromosome Painting
  • Combined Modality Therapy
  • Cytarabine / administration & dosage
  • Drug Resistance, Neoplasm / genetics*
  • Enzyme Inhibitors / therapeutic use*
  • Fatal Outcome
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Amplification*
  • Humans
  • Hydroxyurea / administration & dosage
  • Imatinib Mesylate
  • Interferon-alpha / administration & dosage
  • Karyotyping
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
  • Male
  • Middle Aged
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Peripheral Blood Stem Cell Transplantation
  • Philadelphia Chromosome
  • Piperazines / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Transplantation, Autologous

Substances

  • Antineoplastic Agents
  • Benzamides
  • Enzyme Inhibitors
  • Interferon-alpha
  • Neoplasm Proteins
  • Piperazines
  • Pyrimidines
  • Cytarabine
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • Hydroxyurea