Pharmacogenetics and the treatment of chronic myeloid leukemia: how relevant clinically? An update

Despite the excellent efficacy and improved clinical responses obtained with imatinib mesylate (IM), development of resistance in a significant proportion of chronic myeloid leukemia (CML) patients on IM therapy have emerged as a challenging problem in clinical practice. Resistance to imatinib can b...

Full description

Saved in:
Bibliographic Details
Published in:Pharmacogenomics 2018-04, Vol.19 (5), p.475-393
Main Authors: Ankathil, Ravindran, Azlan, Husin, Dzarr, Abu Abdullah, Baba, Abdul Aziz
Format: Article
Language:English
Subjects:
Apoptosis
BCR-ABL protein
BCR-ABL1 gene
Binding sites
Cancer therapies
Chromosomes
Chronic myeloid leukemia
Disease
Drugs
Genes
Genomes
Genomics
Imatinib
Kinases
Leukemia
Medical prognosis
Myeloid leukemia
Pathogenesis
Patients
Pharmacogenetics
Polymorphism
resistance
response
Signal transduction
SNPs
Targeted cancer therapy
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Despite the excellent efficacy and improved clinical responses obtained with imatinib mesylate (IM), development of resistance in a significant proportion of chronic myeloid leukemia (CML) patients on IM therapy have emerged as a challenging problem in clinical practice. Resistance to imatinib can be due to heterogeneous array of factors involving BCR/ABL-dependent and BCR/ABL-independent pathways. Although BCR/ABL mutation is the major contributory factor for IM resistance, reduced bio-availability of IM in leukemic cells is also an important pharmacokinetic factor that contributes to development of resistance to IM in CML patients. The contribution of polymorphisms of the pharmacogenes in relation to IM disposition and treatment outcomes have been studied by various research groups in numerous population cohorts. However, the conclusions arising from these studies have been highly inconsistent. This review encompasses an updated insight into the impact of pharmacogenetic variability on treatment response of IM in CML patients.
ISSN:1462-2416
1744-8042
DOI:10.2217/pgs-2017-0193