Gender and BCR-ABL transcript type are correlated with molecular response to imatinib treatment in patients with chronic myeloid leukemia

Eur J Haematol. 2016 Apr;96(4):360-6. doi: 10.1111/ejh.12597. Epub 2015 Jul 3.

Abstract

Objectives: Achieving a major molecular response (MMR) is the goal of imatinib therapy for chronic myeloid leukemia. However, the association between gender, BCR-ABL transcript type, and age with MMR is not well understood and often controversial.

Methods: We retrospectively analyzed 166 patients who have been treated with imatinib for up to 10 yr.

Results: Men had a lower MMR rate than women (63.3% vs. 81.6%, P = 0.006) and a shorter time to relapse (median 354 vs. 675 d, P = 0.049), while patients with b3a2 or with both b3a2 and b2a2 break point transcripts had higher MMR rate than those with b2a2 (81.8%, 77.1% vs. 60.7%, P = 0.023 for b3a2 vs. b2a2, P = 0.043 for both vs. b2a2). A striking difference was found between men with b2a2 and women with both b2a2 and b3a2 in terms of MMR rate (43.8% vs. 88.9%), MMR rate within 6 months (7.1% vs. 62.5%) and the time to MMR (median d 493 vs. 159, P = 0.036).

Conclusions: Both gender and BCR-ABL transcript, but not age, were significantly associated with the molecular response. Men with b2a2 represent a less favorable group in their response to imatinib treatment and may need alternative therapy regimen and closer monitoring.

Keywords: BCR-ABL; chronic myeloid leukemia; gender; imatinib; major molecular response.

MeSH terms

  • Adult
  • Aged
  • Alternative Splicing
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism
  • Gene Expression
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / therapeutic use*
  • RNA, Messenger / antagonists & inhibitors*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recurrence
  • Retrospective Studies
  • Sex Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • BCR-ABL1 fusion protein, human
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl