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OCT 1 genetic variants are associated with long term outcomes in imatinib treated chronic myeloid leukemia patients
Author(s) -
KorenMichowitz Maya,
Buzaglo Zehavit,
Ribakovsky Elena,
Schwarz Michaela,
Pessach Ilias,
Shimoni Avichai,
Beider Katia,
Amariglio Ninette,
Ie Coutre Philipp,
Nagler Ar
Publication year - 2014
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12235
Subject(s) - imatinib , genotype , myeloid leukemia , medicine , gastroenterology , incidence (geometry) , imatinib mesylate , biology , gene , genetics , physics , optics
Objectives One third of CML patients treated with first line imatinib have suboptimal responses or treatment failures with increased risk for disease progression. Imatinib is actively transported into cells by the SLC22A1 transporter ( hOCT 1) and its genetic variants may affect intracellular drug import. We studied the effect of SLC22A1 genetic variants on long‐term outcomes of imatinib treated patients. Methods A total of 167 patients, 94% in chronic phase, were analyzed for rs41267797, rs683369, rs12208357, and rs628031 variants using the Sequenom Mass ARRAY platform. Results Rates of CHR, MCyR, CCyR, and MMolR were not significantly different according to allelic variants. However, patients with AA or GA rs628031 genotypes had a higher incidence of poor response to imatinib compared to the GG genotype (47% compared to 29%, P = 0.06), and a higher rate of KD mutation discovery (8/16 vs. 5/27, P = 0.04), suggesting that secondary resistance was more common in these genotypes. Median EFS was shorter for rs628031 genotype AA/AG compared with the GG genotype (61 months and not reached, respectively, P = 0.05), and 5 yr OS rates were lower for patients with the rs628031 genotypes AA/AG compared with the GG genotype (88% and 97%, respectively, P = 0.03). Patients with AA/GA rs628031 and additional rare genotypes had worse EFS and OS compared to patients with only AA/GA rs628031 ( P = 0.02 for EFS and 0.01 for OS). There was no difference in pretreatment SLC22A1 mRNA expression levels in patients with rs628031 genotypes GG/AA or GA. Conclusions Studying SLC 22A1 genetic variants prior to TKI initiation could influence treatment decisions.