[Effects of hOCT1 and ABCB1 gene on the efficacy of imatinib mesylate in chronic myelocytic leukemia]

Zhonghua Yi Xue Za Zhi. 2012 May 29;92(20):1405-8.
[Article in Chinese]

Abstract

Objective: To detect the expression of hOCT1 and ABCB1 in marrow cells and examine the efficacy of imatinib mesylate (IM) in patients with chronic myelocytic leukemia (CML).

Methods: hOCT1 and ABCB1 gene in 90 samples with chronic phase CML diagnosed at our hospital from January 2008 and June 2011 were detected by taqman probe real-time reverse transcription-PCR (RT-PCR). The samples were divided into 3 groups: drug-resistant group (n = 17), partial cytological remission (PCyR) group (n = 11) and complete cytogenetic remission (CCR) group (n = 62) according to IM efficacy and 3 - 6, 7 - 12, 13 - 24, 25 - 48, > 48 months five groups (n = 21, 8, 15, 29, 17) according to IM treatment course. The relationship was explored between two genes and different disease states, course of treatment and time from first CCR.

Results: The hOCT1 gene mRNA expression of CCR group (-3.77 ± 0.55) was higher than drug-resistant group (-4.12 ± 0.47) and PCyR group (-4.24 ± 0.35) (P = 0.047, 0.019). The ABCB1 gene mRNA expression of drug-resistant group (-2.93 ± 0.49) was higher than CCR group (-3.02 ± 0.56) and PCyR group (-3.51 ± 0.45) (P = 0.045, 0.021). The hOCT1 and ABCB1 mRNA expressions showed no significant difference between five groups divided by IM treatment course (P = 0.270, 0.367). The median follow-up time was 30 (3 - 117) months. In same IM treatment course patients, the CCR rates in hOCT1 and ABCB1 low-expression groups were higher than that in high-expression groups separately (P = 0.006, 0.049).

Conclusions: The expression levels of hOCT1 and ABCB1 vary in different disease states of patients on IM. And these two genes may influence the time from first CCR. But there is no significant relationship with course of the treatment.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Child
  • Female
  • Gene Expression Regulation, Leukemic
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Male
  • Middle Aged
  • Organic Cation Transporter 1 / genetics
  • Organic Cation Transporter 1 / metabolism*
  • Piperazines / therapeutic use*
  • Pyrimidines / therapeutic use*
  • RNA, Messenger / genetics
  • Treatment Outcome
  • Young Adult

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Benzamides
  • Organic Cation Transporter 1
  • Piperazines
  • Pyrimidines
  • RNA, Messenger
  • Imatinib Mesylate