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The relation between multidrug resistance gene (MDR1) polymorphism and response to tyrosine kinase inhibitors (TKIS) in patients with chronic myeloid leukemia (CML)

Thesis

Last updated: 06 Feb 2023

Subjects

-

Tags

Internal Medicine

Advisors

Mattar, Mirvat M. , El-Nahhas, Yaser E. , Abdel-Hamid, Asmaa M.

Authors

El-Lithi, Hend Nabil Ahmad

Accessioned

2017-07-12 06:41:11

Available

2017-07-12 06:41:11

type

M.D. Thesis

Abstract

Chronic myeloid leukaemia (CML) is probably one of the most comprehensively studied human malignancies. CML was the first human cancer that responds to molecular target therapy, Imatinib, a member of tyrosine kinase inhibitors (TKIs). Despite the excellent efficacy of TKIs, a subset of patients does not respond to TKIs, and are deemed to have resistance to the drug (Jabbour et al. 2008). Several mechanisms can play a role in the resistance to TKIs but the possible importance of drug-transporter proteins has been only recently appreciated with the demonstration that Imatinib is a substrate of P-glycoprotein (Pgp), the gene product of MDR1 gene. The generally accepted action of MDR1 is to reduce intracellular drug accumulation through Pgp-mediated efflux, thus hampering the achievement of effective drug levels at the target site (Ni L.N et al. 2011). Multi drug resistance gene (MDR1) ABCB1 product is an ATP-driven efflux pump contributing to the pharmacokinetics of drugs that are P-glycoprotein (P-gp) substrates (Eskazan et al. 2011). MDR1 inappropriate expression the P glycoprotein (Pgp) has been frequently implicated in resistance to different chemotherapeutic drugs as MDR1 single nucleotide polymorphisms (SNPs) are associated with drug clearance Imatinib has been reported to be a substrate of the P glycoprotein pump (Dulucq.et al. 2010). Identifying these SNPs may allow predicting drug disposition and responses to TKIs in CML patients.

Issued

1 Jan 2014

DOI

http://dx.doi.org/10.21473/iknito-space/36354

Details

Type

Thesis

Created At

28 Jan 2023