ABCB1 genetic variants in leukemias: current insights into treatment outcomes

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 single-nucleotide polymorphisms (...

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Bibliographic Details
Published in:Pharmacogenomics and personalized medicine 2017-01, Vol.10, p.169-181
Main Author: Ankathil, Ravindran
Format: Article
Language:English
Subjects:
ABCB1 polymorphisms
Bone marrow
Cancer therapies
Care and treatment
Chemotherapy
chemotherapy response
Development and progression
Enzymes
Gene expression
Genetic aspects
Glycoproteins
Haplotypes
Health aspects
Leukemia
Medical prognosis
Patients
Polymorphism
Precision medicine
Radiation therapy
Review
Single nucleotide polymorphisms
survival
Systematic review
Transplants & implants
Transport proteins
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Summary: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 single-nucleotide 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 transporter gene transports a wide range of drugs, including drugs used in leukemia treatment. Polymorphisms in the 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 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.
ISSN:1178-7066
1178-7066
DOI:10.2147/PGPM.S105208