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OCT1 genetic variants are associated with long term outcomes in imatinib treated chronic myeloid leukemia patients.
- Source :
-
European journal of haematology [Eur J Haematol] 2014 Apr; Vol. 92 (4), pp. 283-8. Date of Electronic Publication: 2013 Dec 18. - Publication Year :
- 2014
-
Abstract
- 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 (hOCT1) 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.<br />Methods: A total of 167 patients, 94% in chronic phase, were analyzed for rs41267797, rs683369, rs12208357, and rs628031 variants using the Sequenom MassARRAY platform.<br />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.<br />Conclusions: Studying SLC22A1 genetic variants prior to TKI initiation could influence treatment decisions.<br /> (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Gene Expression
Gene Frequency
Genotype
Humans
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality
Middle Aged
Polymorphism, Single Nucleotide
Prognosis
Treatment Outcome
Young Adult
Antineoplastic Agents therapeutic use
Benzamides therapeutic use
Genetic Variation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Organic Cation Transporter 1 genetics
Piperazines therapeutic use
Protein Kinase Inhibitors therapeutic use
Pyrimidines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0609
- Volume :
- 92
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- European journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 24215657
- Full Text :
- https://doi.org/10.1111/ejh.12235