Polymorphisms in the human organic cation transporter and the multidrug resistance gene: Correlation with imatinib levels and clinical course in patients with chronic myeloid leukemia

Jacob Vine, Sara Bar Cohen, Rosa Ruchlemer, Neta Goldschmidt, Moshe Levin, Diana Libster, Alexander Gural, Moshe E. Gatt, David Lavie, Dina Ben-Yehuda, Deborah Rund*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The optimal tyrosine kinase inhibitor for any individual patient with chronic myeloid leukemia (CML) is not predictable. Pharmacogenetic parameters and trough levels of imatinib (IM) have each been independently correlated with response. We therefore studied the human organic cation transporter (hOCT1) and multidrug resistance (MDR1) single nucleotide polymorphisms (SNPs) and correlated these with IM levels and major molecular response (MMR) (3-log reduction) in 84 patients with CML, the first such study performed in Caucasians. We studied MDR1 G2677T and C3435T, and for hOCT1, C480G and A1222G. IM levels varied significantly with dose (< or > 400 mg/day) (p = 0.038) and were significantly lower in 20 patients who lost MMR (p = 0.042). Adjusting for dose, trough IM levels were not significantly correlated with SNPs. Patients with MDR1 3435 TT had significantly longer times to MMR compared to CC/CT genotypes (p = 0.047). Genotypes did not predict treatment failure when controlling for IM levels. We conclude that IM levels, but not the SNPs studied here, determine IM failure.

Original languageAmerican English
Pages (from-to)2525-2531
Number of pages7
JournalLeukemia and Lymphoma
Volume55
Issue number11
DOIs
StatePublished - 1 Nov 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 Informa UK, Ltd.

Keywords

  • ABCB1
  • Pharmacogenetics
  • Prognosis
  • SLC22A1
  • Tyrosine kinase inhibitors

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