MDR1 gene polymorphisms and imatinib response in chronic myeloid leukemia: A meta-analysis

J Oncol Pharm Pract. 2022 Jan;28(1):39-48. doi: 10.1177/1078155220981150. Epub 2021 Feb 10.

Abstract

Background: Our study aimed to investigate the association between multidrug resistance (MDR1) C1236T, C3435T and G2677T/A polymorphisms and the response to imatinib (IM) in chronic myeloid leukemia (CML).

Materials and methods: An electronic databases in PubMed, Embase, Web of Knowledge, Scopus and Cochrane were searched using combinations of keywords relating to MDR1 polymorphisms and the response to IM in CML. Studies retrieved from database searches were screened using strict inclusion and exclusion criteria.

Results: In total, 37 studies were initially identified, and 17 studies, involving 4494 CML patients, were eventually included in this meta-analysis.Results of our study revealed significant association between MDR1 G2677T/A and C3435T polymorphisms and response to IM in Caucasian population under recessive model (T or A vs G; OR = 1.43,95%CI [1;06-1.93]; T vs C;OR = 1.13; 95%IC [0.79; 1.63]), dominant (T or A vs G; OR = 0.94; 95%CI [0.74-1.21]; T vs C; OR = 1.49; 95%CI [1.02-2.17]) and heterozygous models (T or A vs G; OR = 0.83; 95%CI [0.64; 1.09]; T vs C; OR = 1.52; 95%CI [1.01-2.28]); respectively. However, never significative association was found between IM response and the MDR1 C1236T polymorphism (OR = 1.25; 95%CI [0.46; 3.33]).

Conclusion: The MDR1 G2677T/A and C3435T polymorphisms might be a risk factor for resistance to IM in Caucasian CML patients.

Keywords: Chronic myeloid leukemia; imatinib mesylate; multidrug resistance gene; polymorphisms.

Publication types

  • Meta-Analysis

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Genotype
  • Humans
  • Imatinib Mesylate* / therapeutic use
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Polymorphism, Single Nucleotide*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Imatinib Mesylate