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

Author:

Ankathil Ravindran1,Azlan Husin2,Dzarr  Abu Abdullah2,Baba Abdul Aziz3

Affiliation:

1. Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

2. Haemato-Oncology Unit & Department of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

3. Department of Medicine, International Medical University, Kuala Lumpur, Malaysia

Abstract

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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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