Association of the hOCT1/ABCB1 genotype with efficacy and tolerability of imatinib in patients affected by chronic myeloid leukemia

Cancer Chemother Pharmacol. 2017 Apr;79(4):767-773. doi: 10.1007/s00280-017-3271-3. Epub 2017 Mar 13.


Purpose: The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia.

Methods: Through a procedure based on a sequence of classical statistics methods, we investigated the possible relationships between treatment efficacy/tolerability and combinations of time-independent variables as gender and genetic covariates in the form of single nucleotide polymorphisms (SNPs) or combinations thereof. Moreover, since the drug tolerability has a strong incidence on the discontinuation of the therapy, we investigated whether the time of manifestation of the most frequent toxic effects can be related to time-independent patients' characteristics or not.

Results: We found that a combination of two polymorphisms, namely hOCT1 c.480C>G (rs683369) and ABCB1 c.3435C>T (rs1045642), seems to play the role of predictor for imatinib in both efficacy and toxicity. Furthermore, the time of manifestation of edema toxicity is found to be associated to a combination of gender and ABCB1 c.3435C>T, whereas the time of manifestation of cramp toxicity appears related to gender.

Conclusions: The novelty of this study is dual: the achievement of results that potentially have a significant clinical interest and the demonstration that the adoption of composed covariates may represent a unique tool to study different aspects of the treatment with imatinib.

Keywords: ABCB1; Complete cytogenetic response; Factor analysis of mixed data; Imatinib; Tolerability; hOCT1.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use*
  • Edema / chemically induced
  • Edema / genetics
  • Factor Analysis, Statistical
  • Female
  • Genotype
  • Humans
  • Imatinib Mesylate / adverse effects*
  • Imatinib Mesylate / therapeutic use*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Middle Aged
  • Muscle Cramp / chemically induced
  • Muscle Cramp / genetics
  • Octamer Transcription Factor-1 / genetics*
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Prognosis
  • Sex Characteristics


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • Imatinib Mesylate