Ankathil, Ravindran
(2017)
ABCB1 genetic variants in leukemias: current insights into treatment outcomes.
Pharmacogenomics and Personalized Medicine, 12 (10).
pp. 169-181.
ISSN 1178-7066
Abstract
Despite improvements in treatment of different types of leukemia, not all patients
respond optimally for a particular treatment. Some treatments will work better for some, while
being harmful or ineffective for others. This is due to genetic variation in the form of singlenucleotide
polymorphisms (SNPs) that affect gene expression or function and cause inherited
interindividual differences in the metabolism and disposition of drugs. Drug transporters are
one of the determinants governing the pharmacokinetic profile of chemotherapeutic drugs. The
ABCB1 transporter gene transports a wide range of drugs, including drugs used in leukemia
treatment. Polymorphisms in the ABCB1 gene do affect intrinsic resistance and pharmacokinetics
of several drugs used in leukemia treatment protocols and thereby affect the efficacy of treatment
and event-free survival. This review focuses on the impact of three commonly occurring SNPs
(1236C>T, 2677G>T/A, and 3435C>T) of ABCB1 on treatment response of various types of
leukemia. From the literature available, some of the genotypes and haplotypes of these SNPs
have been found to be potential determinants of interindividual variability in drug disposition
and pharmacologic response in different types of leukemia. However, due to inconsistencies in
the results observed across the studies, additional studies, considering novel genomic methodologies,
comprehensive definition of clinical phenotypes, adequate sample size, and uniformity
in all the confounding factors, are warranted.
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