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ABCB1 gene polymorphisms are not associated with treatment outcome in elderly acute myeloid leukemia patients

Bronno van der Holt1, Marry M Van den Heuvel-Eibrink, Ron H N Van Schaik

  • 1Department of Trials & Statistics-HOVON (Dutch-Belgian Hemato-Oncology Cooperative Group) Data Center, Erasmus MC-Daniel den Hoed Cancer Center and Sophia Children's Hospital, Rotterdam, The Netherlands. b.vanderholt@erasmusmc.nl

Clinical Pharmacology and Therapeutics
|November 23, 2006
PubMed
Abstract

Insights

Single-nucleotide polymorphisms in the ABCB1 gene do not impact P-glycoprotein function or expression in older acute myeloid leukemia patients. These genetic variations do not significantly affect treatment outcomes or prognosis in this patient group.

Area of Science:

  • Pharmacogenomics
  • Hematologic Malignancies
  • Molecular Biology

Background:

  • The multidrug resistance gene MDR1 (ABCB1) encodes P-glycoprotein (P-gp), an efflux pump associated with poor prognosis in acute myeloid leukemia (AML), particularly in older patients.
  • Specific single-nucleotide polymorphisms (SNPs) in ABCB1 (C1236T, G2677T, C3435T) have been linked to altered drug metabolism and treatment outcomes.

Purpose of the Study:

  • To prospectively investigate the association between ABCB1 SNPs (C1236T, G2677T, C3435T) and P-gp function/expression in AML blasts from elderly patients (≥60 years).
  • To evaluate the correlation of these SNPs with ABCB1 mRNA levels and clinical outcomes, including response rates and survival.

Main Methods:

  • Analysis of purified leukemic blasts from 150 elderly AML patients diagnosed in a multicenter, randomized phase 3 trial.
  • Evaluation of the significance of ABCB1 allelic variants (C1236T, G2677T, C3435T) concerning P-gp expression and function, and ABCB1 mRNA levels.
  • Correlation of genetic variants with treatment response and survival endpoints.

Main Results:

  • No significant variations in P-gp function, expression, or ABCB1 mRNA levels were observed among the different allelic variants of ABCB1.
  • None of the studied allelic variations demonstrated predictive value for complete response rates or survival outcomes.

Conclusions:

  • In elderly AML patients (≥60 years), ABCB1 SNPs C1236T, G2677T, and C3435T are not associated with altered P-gp function or MDR1 expression at the mRNA or protein level in leukemic cells.
  • These specific ABCB1 genetic variations do not significantly influence the clinical prognosis of older patients with AML.

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