Three single-nucleotide polymorphisms (C1236T, G2677T/A, C3435T) and/or mRNA expression changes of ABCB1 gene were demonstrated to be associated with inter-individual variability of imatinib response in CML patients.
Influence of MDR1 and CYP3A5 genetic polymorphisms on trough levels and therapeutic response of imatinib in newly diagnosed patients with chronic myeloid leukemia.
We therefore studied the human organic cation transporter (hOCT1) and multidrug resistance (MDR1) single nucleotide polymorphisms (SNPs) and correlated these with IM levels and major molecular response (MMR) (3-log reduction) in 84 patients with CML, the first such study performed in Caucasians.
An electronic databases in PubMed, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and VIP were searched using combinations of keywords relating to MDR1 polymorphisms and the response to IM in CML.
This study, therefore, investigated the influence of CYP3A5*3, ABCG2 421C>A and ABCB1 3435 C>T genetic polymorphism on the clinical outcome and steady-state trough plasma concentration (TPC) of imatinib in Nigerians with CML.
However, no significant association was found for the MDR1G2677T or C3435T polymorphisms in an Asian CML population as well as a Caucasian CML population.
In the present study we evaluated the association of eight polymorphisms in the seven genes CYP3A5*3 (rs776746), CYP3A4*1 (rs2740574), CYP2C9*3 (rs1057910), SLC22A1 (rs683369), ABCB1 (rs1045642, rs1128503), ABCG2 (rs2231142) and ABCC2 (rs717620) with imatinib plasma level and achieving an optimal clinical response in 112 CML patients (53 men and 59 women).
The present study aimed to conduct a series of meta-analyses to investigate the influence of imatinib trough concentration (C<sub>0</sub>), as well as ABCB1 and ABCG2 polymorphisms, on the clinical response in patients with chronic myeloid leukemia (CML).
Three ABCB1 SNPs (C1236T, G2677T, and C3435T) were genotyped in 100 Egyptian patients with CML undergoing IM therapy using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.
A chronic myeloid leukemia (CML) in blast crisis, however, showed combined increases in mdr1 (about 20-fold) and mrp (about four fold) gene expression after intense but unsuccessful chemotherapy over a 6-month period.
To investigate the interplay between these three modes of resistance, three CML blast crisis cell lines (K562, its ABCB1-overexpressing variant K562 Dox, and KU812) were cultured in gradually increasing concentrations of imatinib to 2 μM, or dasatinib to 200 nM.
We have developed a preclinical model of MDR/CML uncomplicated by other mechanisms of drug resistance to evaluate the effects of MDR1 overexpression on cytodestructive and differentiation therapy and the ability of sensitizers to restore chemosensitivity in this disease.
Development of multidrug resistance (MDR) is a continuous clinical challenge partially due to the overexpression of P-glycoprotein (P-gp) for chronic myelogenous leukemia (CML) patients.