Association of genetic polymorphisms of the ABCG2, ABCB1, SLCO1B3 genes and the response to Imatinib in chronic myeloid leukemia patients with chronic phase

Nair, Devika; Dhangar, Somprakash; Shanmukhaiah, Chandrakala; Vundinti, Babu Rao

doi:10.1016/j.mgene.2016.11.002

Cited by 7 publications

(9 citation statements)

References 18 publications

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“…Our data showed a significant association of the genotype TT of SLCO1B3 334 T>G with higher risk of unfavorable response ( P = 0.03), while the patients with (GT/GG) genotypes showed a higher probability of achieving a favorable response ( P = 0.03). Our finding agrees with the study of Nair et al ( 42 ). Contrary to the previous result, the (TT) genotype was more frequent in the responder group ( P = 0.042) and carriers of (TG/GG) genotypes were more frequent in the non-responder group ( 43 ).…”

Section: Discussionsupporting

confidence: 94%

Association of the Trough, Peak/Trough Ratio of Imatinib, Pyridine–N-Oxide Imatinib and ABCG2 SNPs 34 G>A and SLCO1B3 334 T>G With Imatinib Response in Egyptian Chronic Myeloid Leukemia Patients

et al. 2020

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Imatinib mesylate (IM) is highly efficacious in the treatment of chronic myeloid leukemia (CML). Therapeutic drug monitoring and pharmacogenetic screening are affirmed for better management of IM therapy. The goal of this study was to gain a greater mechanistic understanding of the factors controlling variability in IM level and its relation to the response. One hundred and two patients with CML at chronic phase were recruited in this study. Blood samples were withdrawn at least 30 days after drug administration, and trough and peak concentrations of imatinib, N-des-methyl imatinib, and pyridine-N-oxide imatinib were determined by HPLC/MS/MS. Genetic polymorphism of the genes ABCG2 SNPs 34 G>A and 421C >A; ABCB1 SNPs 2677 G>A/T, 1236 C>T, 3435 C>T; SLCO1B3 SNPs 334 T>G and CYP3A5 were studied using PCR-RFLP technique. Our study presented significant higher trough IM (1,281 ± 578 ng/ml), lower Peak/Trough ratio, clearance (Cl), and elimination rate constant, k e , among patients who achieved favorable responses ( N = 64) than those for patients who suffered unfavorable response ( N = 37). The P/T ratio was the only significant independent factor affecting response, as the P/T ratio increased by one, the risk of unfavorable response increased by more than double as compared to favorable response with 95% CI (1.28–3.92, P = 00.005). Moreover, like the results of IM, the trough concentration of Pyridine-N-oxide imatinib was significantly higher ( P = 0.01) and its P/T ratio was significantly lower ( P = 0.008) in patients achieved favorable response than those without. The wild GG genotype of the ABCG2.34 G>A gene was associated with favorable response ( P = 0.01), lower Cl, K e and high plasma IM trough level than both (AA+GA) genotypes. ABCG2.421C >A (CC) genotype had a significantly higher plasma peak of IM, N-des-methyl imatinib and higher C ss . The GG and TG alleles of the SLCO1B3.334 T>G gene were significantly correlated to favorable response, while the wild allele TT was linked to unfavorable response ( P = 0.03). In conclusion, the trough and P/ T ratio for both IM and Pyridine-N-oxide imatinib, in addition to Polymorphism of ABCG2 SNPs 34 G>A and SLCO1B3.334 T>G gene, is a good predictor for response of IM in CML Egyptian patients.

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Section: Discussionsupporting

confidence: 94%

Association of the Trough, Peak/Trough Ratio of Imatinib, Pyridine–N-Oxide Imatinib and ABCG2 SNPs 34 G>A and SLCO1B3 334 T>G With Imatinib Response in Egyptian Chronic Myeloid Leukemia Patients

et al. 2020

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“…Our results is also in accordance with the findings of Au et al [5] , Dulucq et al [18] , and Deenik et al [22] who reported that the patients with 1236CC genotype were associated with IM resistance, and those with 1236TT genotype showed higher probability to achieve IM response. In contrast, in several studies, no association was found between 1236CT and 3435CT genotypes and IM response [13,23,24] . Regarding the c.3435 CC genotype, Lardo et al [25] found the association of this genotype with the complete molecular response, while Ni et al [26] SNP/ gen. indicated the association of c.3435TT with the increased risk of IM resistance.…”

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 82%

“…The P-gp may contribute to mutagenesis via the cumulation of exogenous toxins in cells and increase the risk of cancer [ 11 , 12 ] . Some investigations have reported that the overexpression of P-gp enhances the clearance of the drug, resulting in decrease drug availability in the cells and confer resistance to IM [ 8 , 13 ] . IM is a substrate for ABCB1 transporter, and ABCB1 polymorphisms may influence the pharmacokinetic and intracellular concentration of IM.…”

Section: Introductionmentioning

confidence: 99%

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Impact of ABCB1 Gene Polymorphisms and Smoking on the Susceptibility Risk of Chronic Myeloid Leukemia and Cytogenetic Response

Mohammadi

Shafiei

Assad

et al. 2021

ibj

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“…Polymorphism of OATP1B3, which is encoded by SLCO1B3, can also influence therapeutic outcome of imatinib. In Indian patients SLCO1B3 334TT genotype was found to be significantly related with a higher risk of failure of cytogenetic response at 12 months though there was no significant difference in molecular response (MR) at 18 months [18]. In a study conducted in Brazil, SLCO1B3 699GG and 344TT genotypes were significantly associated with good imatinib response and carriers of 699GA/AA and 334TG/GG genotypes had significantly low chance of responding to standard dose of imatinib [19].…”

Section: Impact Of Oct1 On Clinical Outcomesmentioning

confidence: 95%

Pharmacology of tyrosine kinase inhibitors in chronic myeloid leukemia; a clinician’s perspective

Pushpam

Bakhshi

2020

DARU J Pharm Sci

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Objective In this review, we have summarized the pharmacokinetics, pharmacodynamics and adverse effects of imatinib, dasatinib, nilotinib, bosutinib, ponatinib and radotinib with focus on pharmacogenomic studies with clinical end points. We have discussed the key phase 3 trials of tyrosine kinase inhibitors (TKI) comparing with each other, treatment free remission (TFR) and selection of TKI. Upcoming concepts and related trials in the management of chronic myeloid leukemia (CML) along with future directions have been touched upon. Evidence acquisition PubMed, Embase, Google, Cochrane library and Medline were searched to identify relevant literature for the review. Clinicaltrial.gov was searched for upcoming data and trials. Results There are lot of gap in pharmacokinetics and pharmacodynamics of TKI. Imatinib appears to be the safest TKI. Newer TKI's achieve better achievement of therapeutic milestones, deeper molecular response and less chances of progression of CML compared to imatinib. Newer TKI appears to be better choice for achieving TFR. When the objective is survival, imatinib is still the TKI of choice. Primary prophylaxis with antiplatelet drugs for TKI having cardiovascular and thromboembolic side effects should be considered. Conclusion Pharmacogenetic data of TKI is still immature to guide in therapeutic decision making in clinical practice. There is need for further research in pharmacology and pharmacogenomics of newer TKI's. Randomized controlled trials are required to decide the optimum TKI for TFR. Safe and effective TKI for targeting T315I mutation, CML accelerated phase and blast crisis are an active area of research.

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Association of genetic polymorphisms of the ABCG2, ABCB1, SLCO1B3 genes and the response to Imatinib in chronic myeloid leukemia patients with chronic phase

Cited by 7 publications

References 18 publications

Association of the Trough, Peak/Trough Ratio of Imatinib, Pyridine–N-Oxide Imatinib and ABCG2 SNPs 34 G>A and SLCO1B3 334 T>G With Imatinib Response in Egyptian Chronic Myeloid Leukemia Patients

Association of the Trough, Peak/Trough Ratio of Imatinib, Pyridine–N-Oxide Imatinib and ABCG2 SNPs 34 G>A and SLCO1B3 334 T>G With Imatinib Response in Egyptian Chronic Myeloid Leukemia Patients

Impact of ABCB1 Gene Polymorphisms and Smoking on the Susceptibility Risk of Chronic Myeloid Leukemia and Cytogenetic Response

Pharmacology of tyrosine kinase inhibitors in chronic myeloid leukemia; a clinician’s perspective

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