ABCB1 1199G > A polymorphism (rs2229109) affects the transport of imatinib, nilotinib and dasatinib

作者：Dessilly Geraldine; Elens Laure; Panin Nadtha; Karmani Linda; Demoulin Jean Baptiste; Haufroid Vincent^*

来源：Pharmacogenomics, 2016, 17(8): 883-890.

DOI：10.2217/pgs-2016-0012

• ABCB1
• ABCB1 1199G > A
• dasatinib
• HEK293
• imatinib
• K562
• nilotinib
• SNP

Aim: ABCB1 (or P-glycoprotein) is implicated in the multidrug-resistance phenotype, including the resistance toward anticancer drugs such as tyrosine kinase inhibitors (TKIs). The purpose of this study was to evaluate in vitro the influence of the ABCB1 1199G>A SNP on ABCB1 transport activity toward selected TKIs (imatinib, nilotinib and dasatinib) that are currently used in chronic myelogenous leukemia. Material & methods: Two different cell lines, HEK293 and K562, were stably transfected with ABCB1 1199G wild-type or ABCB1 1199A variant allele. The impact of this polymorphism on accumulation and antiproliferative effects of imatinib, nilotinib and dasatinib was evaluated. Results: In K562 models, the expression of Asn400 variant protein was associated with lower antiproliferative effects of imatinib, nilotinib and dasatinib compared with Ser400 wild-type protein. Moreover, in HEK293 cells, imatinib and nilotinib intracellular accumulation were lower in variant compared with wild-type models. Conclusion: Imatinib, nilotinib and dasatinib are transported more efficiently by the ABCB1 variant (Asn400) compared with the wild-type (Ser400) protein. The impact of ABCB1 1199G>A SNP on TKI response should be further investigated in chronic myelogenous leukemia patients.

• 出版日期2016-6