Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia

被引：191

作者：

Dulucq, Stephanie ^{[1
]}

Bouchet, Stephane ^{[2
,3
]}

Turcq, Beatrice ^{[1
]}

Lippert, Eric ^{[1
]}

Etienne, Gabriel ^{[4
]}

Reiffers, Josy ^{[4
]}

Molimard, Mathieu ^{[2
,3
]}

Krajinovic, Maja ^{[5
]}

Mahon, Francois-Xavier ^{[1
]}

机构：

[1] Univ Bordeaux 2, Lab Hematopoiese Leucemique & Cible Therapeut, INSERM, U876, F-33076 Bordeaux, France

[2] CHU, Dept Clin Pharmacol & Toxicol, Bordeaux, France

[3] INSERM, U657, Bordeaux, France

[4] Reg Canc Ctr, Inst Bergonie, Dept Hematol, Bordeaux, France

[5] Univ Montreal, Dept Pediat & Pharmacol, CHU St Justine, Res Ctr, Cote Ste Catherine, PQ, Canada

来源：

BLOOD | 2008年 / 112卷 / 05期

关键词：

D O I：

10.1182/blood-2008-03-147744

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Despite the excellent efficacy of imatinib in chronic myeloid leukemia (CML), the response in patients is heterogeneous, which may in part be caused by pharmacogenetic variability. Imatinib has been reported to be a substrate of the P-glycoprotein pump. In the current study, we focused on the ABCB1 (MDR1) genotype. We analyzed the 3 most relevant single nucleotide polymorphisms of MDR1 in 90 CML patients treated with imatinib. Among the patients homozygous for allele 1236T, 85% achieved a major molecular response versus 47.7% for the other genotypes (P =.003). For the 2677G>T/A polymorphism, the presence of G allele was associated with worse response (77.8%, TT/TA; vs 47.1%, GG/GA/GT; P =.018). Patients with 1236TT genotype had higher imatinib concentrations. One of the haplotypes (1236C-2677G-3435C) was statistically linked to less frequent major molecular response (70% vs 44.6%; P =.021). Hence, we demonstrated the usefulness of these single nucleotide polymorphisms in the identification of CML who may or may not respond optimally to imatinib.

引用

页码：2024 / 2027

页数：4

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