No significance of derivative chromosome 9 deletion on the clearance kinetics of BCR/ABL fusion transcripts, cytogenetic or molecular response, loss of response, or treatment failure to imatinib mesylate therapy for chronic myeloid leukemia

Cancer. 2008 Aug 15;113(4):772-81. doi: 10.1002/cncr.23607.

Abstract

Background: Although deletion of the derivative chromosome 9 (der 9; del-der 9) carries a poor prognosis in patients with chronic myeloid leukemia (CML) who are treated with hydroxyurea or interferon, its significance in patients on imatinib mesylate (IM) therapy is debated.

Methods: In the current study, the authors used a locus-specific indicator breakpoint cluster region/receptor tyrosine kinase (BCR/ABL) probe to evaluate the significance of del-der 9 in 163 patients with CML who had fluorescence in situ hybridization (FISH) results available. Serial changes in BCR/ABL fusion transcript levels also were monitored by using messenger RNA (mRNA) quantitative polymerase chain reaction (PCR).

Results: Of 163 patients, 22 (13.5%) had del-der 9 before commencing IM therapy. No differences were noted in the time to hematologic response (P = .598), major cytogenetic response (CyR) (P = .281), complete CyR (P = .883), major molecular response (MoR) (P = .125), or complete MoR (P = .834). In addition, the times to loss of response (LOR) (P = .974), treatment failure (P = .455; including primary hematologic or cytogenetic resistance and LOR), transformation-free survival (P = .276), and dose escalation of IM (P = .816) did not differ significantly between patients with and without del-der 9. The results of serial BCR/ABL mRNA quantitative PCR revealed similar patterns of BCR/ABL fusion gene reduction between the 2 groups.

Conclusions: The presence of del-der 9 in patients with CML did not influence 1) the response to IM therapy in terms of hematologic response, CyR, or MoR; 2) LOR; 3) treatment failure; 4) progression to accelerated phase/blast crisis; or 5) time to dose escalation of IM. Therefore, the authors concluded that the detection of del-der 9 does not have an impact on the current management of patients with CML who are receiving IM therapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Benzamides
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 9*
  • Female
  • Fusion Proteins, bcr-abl / metabolism*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / therapeutic use*
  • Pyrimidines / administration & dosage
  • Pyrimidines / therapeutic use*
  • RNA, Messenger / analysis
  • Retrospective Studies
  • Treatment Failure
  • Treatment Outcome

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • RNA, Messenger
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl