Correlation between genetic polymorphisms of the hOCT1 and MDR1 genes and the response to imatinib in patients newly diagnosed with chronic-phase chronic myeloid leukemia

Margherita Maffioli; Mireia Camós; Anna Gaya; Juan-Carlos Hernández-Boluda; Alberto Alvarez-Larrán; Abel Domingo; Miquel Granell; Vicent Guillem; Rolando Vallansot; Dolors Costa; Beatriz Bellosillo; Dolors Colomer; Francisco Cervantes

doi:10.1016/j.leukres.2010.12.004

Correlation between genetic polymorphisms of the hOCT1 and MDR1 genes and the response to imatinib in patients newly diagnosed with chronic-phase chronic myeloid leukemia

Leuk Res. 2011 Aug;35(8):1014-9. doi: 10.1016/j.leukres.2010.12.004. Epub 2010 Dec 24.

Authors

Margherita Maffioli¹, Mireia Camós, Anna Gaya, Juan-Carlos Hernández-Boluda, Alberto Alvarez-Larrán, Abel Domingo, Miquel Granell, Vicent Guillem, Rolando Vallansot, Dolors Costa, Beatriz Bellosillo, Dolors Colomer, Francisco Cervantes

Affiliation

¹ Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.

PMID: 21185600
DOI: 10.1016/j.leukres.2010.12.004

Abstract

The association between seven polymorphisms in the genes hOCT1 and MDR1, encoding for imatinib transporter proteins, and the response to imatinib 400mg/daily was investigated in 65 patients newly diagnosed with chronic-phase chronic myeloid leukemia. The AA genotype at the rs6935207 hOCT1 polymorphic locus was not detected in patients with inadequate response to imatinib. The CC genotype at the rs1045642 (C3435T) MDR1 locus was associated with primary failure, whereas a T allele at the rs2032582 (G2677T/A) MDR1 locus seemed to protect from primary failure. Beside, the MDR1 haplotype 1236T-2677G-3435C was more frequently found in patients primarily resistant to imatinib.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
Adult
Aged
Benzamides
DNA, Neoplasm / genetics
Female
Follow-Up Studies
Genotype
Haplotypes / genetics
Humans
Imatinib Mesylate
Leukemia, Myeloid, Chronic-Phase / drug therapy*
Leukemia, Myeloid, Chronic-Phase / genetics*
Male
Middle Aged
Organic Cation Transporter 1 / genetics*
Piperazines / therapeutic use*
Polymerase Chain Reaction
Polymorphism, Genetic / genetics*
Pyrimidines / therapeutic use*
Survival Rate
Treatment Outcome
Young Adult

Substances

ABCB1 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
Benzamides
DNA, Neoplasm
Organic Cation Transporter 1
Piperazines
Pyrimidines
Imatinib Mesylate