Influence of CYP3A5*3 and ABCB1 C3435T on clinical outcomes and trough plasma concentrations of imatinib in Nigerians with chronic myeloid leukaemia

Adeagbo, Babatunde Ayodeji; Bolaji, Oluseye O.; Olugbade, T. A.; Durosinmi, M. A.; Bolarinwa, Rahman A.; Masimirembwa, Collen

doi:10.1111/jcpt.12424

Cited by 25 publications

(28 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They showed a higher resistance rate than those with the CC genotype [ 58 ]. In contrast, some (not statistically significant) data suggested higher frequencies of MMR related to 3435TT in a Nigerian cohort with 110 CP CML patients [ 61 ]. More contradictory observations were found with genotype 3435CC.…”

Section: Abcb1 Polymorphisms (Snps) In Chronic mentioning

confidence: 99%

“…Dulucq et al have shown that higher concentrations of IM correlated with the homozygous 1236T allele and MMR after 12 months of treatment with IM [ 54 ]. In a Nigerian population, Adeagbo et al [ 61 ] reported that the C3435T genotype was associated with higher concentrations of IM. In a Caucasian population, Galeotti et al [ 77 ] found the same SNP as being predictive of IM efficacy and toxicity.…”

Section: Abcb1 Polymorphisms (Snps) In Chronic mentioning

confidence: 99%

See 1 more Smart Citation

Towards Comprehension of the ABCB1/P-Glycoprotein Role in Chronic Myeloid Leukemia

et al. 2018

View full text Add to dashboard Cite

The introduction of imatinib (IM), a BCR-ABL1 tyrosine kinase inhibitor (TKI), has represented a significant advance in the first-line treatment of chronic myeloid leukemia (CML). However, approximately 30% of patients need to discontinue IM due to resistance or intolerance to this drug. Both resistance and intolerance have also been observed in treatment with the second-generation TKIs—dasatinib, nilotinib, and bosutinib—and the third-generation TKI—ponatinib. The mechanisms of resistance to TKIs may be BCR-ABL1-dependent and/or BCR-ABL1-independent. Although the role of efflux pump P-glycoprotein (Pgp), codified by the ABCB1 gene, is unquestionable in drug resistance of many neoplasms, a longstanding question exists about whether Pgp has a firm implication in TKI resistance in the clinical scenario. The goal of this review is to offer an overview of ABCB1/Pgp expression/activity/polymorphisms in CML. Understanding how interactions, associations, or cooperation between Pgp and other molecules—such as inhibitor apoptosis proteins, microRNAs, or microvesicles—impact IM resistance risk may be critical in evaluating the response to TKIs in CML patients. In addition, new non-TKI compounds may be necessary in order to overcome the resistance mediated by Pgp in CML.

show abstract

Section: Abcb1 Polymorphisms (Snps) In Chronic mentioning

confidence: 99%

Section: Abcb1 Polymorphisms (Snps) In Chronic mentioning

confidence: 99%

Towards Comprehension of the ABCB1/P-Glycoprotein Role in Chronic Myeloid Leukemia

et al. 2018

View full text Add to dashboard Cite

show abstract

“…No studies have assessed drug pharmacokinetics on the Central African population, although one study has evaluated genetic polymorphisms and the influence on imatinib blood levels in a West African population. It found that Nigerians were more likely to have genotypes that were associated with lower trough drug levels, however even between ethnic tribes allelic frequencies were significantly different [ 18 ]. Thus, it is clear that in areas endemic to Loa loa infection in Central Africa that more work still needs to be done in assessing imatinib pharmacokinetics in this population.…”

Section: Discussionmentioning

confidence: 99%

Defining the target and the effect of imatinib on the filarial c-Abl homologue

et al. 2017

View full text Add to dashboard Cite

BackgroundPreviously we demonstrated the micro- and macrofilaricidal properties of imatinib in vitro. Here we use electron and multiphoton microscopy to define the target of imatinib in the adult and microfilarial stages of Brugia malayi and assess the effects of pharmacologically relevant levels of imatinib on the adult parasites.MethodsAfter fixation of adult B. malayi males and females, sections were stained with polyclonal rabbit anti-c-Abl antibody (or isotype control) and imaged with multiphoton fluorescent microscopy. Microfilariae were fixed and labeled with rabbit anti-c-Abl IgG primary antibody followed by anti-rabbit gold conjugated secondary antibody and imaged using transmission electron microscopy (TEM; immunoEM). In addition, adult B. malayi males and females were exposed to 0 or 10μM of imatinib for 7 days following which they were prepared for transmission electron microscopy (TEM) to assess the drug’s effect on filarial ultrastructure.ResultsFluorescent localization of anti-c-Abl antibody demonstrated widespread uptake in the adult filariae, but the most intense signal was seen in the reproductive organs, muscle, and intestine of both male and female worms. Fluorescence was significantly more intense in the early microfilarial stage (i.e. early morula) compared with later development stages (i.e. pretzel). Anti-c-Abl antibody in the microfilariae localized to the nuclei. Based on TEM assessment following imatinib exposure, imatinib appeared to be detrimental to embryogenesis in the adult female B. malayi.ConclusionsAt pharmacologically achievable concentrations of imatinib, embryogenesis is impaired and possibly halted in adult filariae. Imatinib is likely a slow microfilaricide due to interference in intra-nuclear processes, which are slowly detrimental to the parasite and not immediately lethal, and thus may be used to lower the levels of L. loa microfilariae before they are treated within the context of conventional mass drug administration.

show abstract

“…Aims to collect essential information about the structure of African genomes to provide a basic framework for genetic disease studies in Africa https://www.sanger.ac.uk /science/collaboration/ african-genome-variation-project (Adeagbo et al, 2016), and the pharmacokinetics of rosuvastatin in African populations (Soko et al, 2016;Soko et al, 2018) and showed the potential importance of pharmacogenetic biomarkers in the optimal use of these drugs in African populations.…”

Section: African Genome Variation Projectmentioning

confidence: 99%

African Pharmacogenomics Consortium: Consolidating pharmacogenomics knowledge, capacity development and translation in Africa

et al. 2019

View full text Add to dashboard Cite

The African Pharmacogenomics Consortium (APC) was formally launched on the 6th September 2018. This white paper outlines its vision, and objectives towards addressing challenges of conducting and applying pharmacogenomics in Africa and identifies opportunities for advancement of individualized drugs use on the continent. Africa, especially south of the Sahara, is beset with a huge burden of infectious diseases with much co-morbidity whose multiplicity and intersection are major challenges in achieving the sustainable development goals (SDG), SDG3, on health and wellness. The profile of drugs commonly used in African populations lead to a different spectrum of adverse drug reactions (ADRs) when compared to other parts of the world. Coupled with the genetic diversity among Africans, the APC is established to promote pharmacogenomics research and its clinical implementation for safe and effective use of medicine in the continent. Variation in the way patients respond to treatment is mainly due to differences in activity of enzymes and transporters involved in pathways associated with each drug’s disposition. Knowledge of pharmacogenomics, therefore, helps in identifying genetic variants in these proteins and their functional effects. Africa needs to consolidate its pharmacogenomics expertise and technological platforms to bring pharmacogenomics to use.

show abstract

Influence of CYP3A5*3 and ABCB1 C3435T on clinical outcomes and trough plasma concentrations of imatinib in Nigerians with chronic myeloid leukaemia

Abstract: This is the first pharmacogenetics study of CML patients in the Nigerian population with ethnic differences in the distribution of ABCB1 C3435T. Genetic polymorphisms in CYP3A5*3 and ABCB1 C3435T are associated with TPC in CML patients in this population.

Cited by 25 publications

References 32 publications

Towards Comprehension of the ABCB1/P-Glycoprotein Role in Chronic Myeloid Leukemia

Towards Comprehension of the ABCB1/P-Glycoprotein Role in Chronic Myeloid Leukemia

Defining the target and the effect of imatinib on the filarial c-Abl homologue

African Pharmacogenomics Consortium: Consolidating pharmacogenomics knowledge, capacity development and translation in Africa

Contact Info

Product

Resources

About