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. 2024 Dec 23;95(1):12.
doi: 10.1007/s00280-024-04723-y.

Influence of CYP2C8*3 and ABCG2 C421A genetic polymorphisms on trough concentration and molecular response of imatinib in Egyptian patients with chronic myeloid leukemia

Safwat A Mangoura  1   2 , Mahmoud H Abdel-Raheem  2 , Hanan A Eltyb  3 , Mohammed S Molla  4 , Abeer M R Hussein  2
Affiliations

Influence of CYP2C8*3 and ABCG2 C421A genetic polymorphisms on trough concentration and molecular response of imatinib in Egyptian patients with chronic myeloid leukemia

Safwat A Mangoura et al. Cancer Chemother Pharmacol. .

Abstract

Purpose: The treatment landscape for chronic myeloid leukemia (CML) has been revolutionized by the introduction of imatinib, a tyrosine kinase inhibitor, which has transformed the disease from a fatal condition into a manageable chronic illness for a substantial number of patients. Despite this, some individuals do not respond adequately to the treatment, and others may experience disease progression even with continued therapy. This study examined how CYP2C8*3 (G416A; rs11572080) and ABCG2 C421A (rs2231142) single nucleotide polymorphisms (SNPs) affect the plasma trough concentration and therapeutic response of imatinib in Egyptian CML patients.

Methods: The study included fifty patients with chronic-phase CML, who were categorized into two groups: responders (n = 26) and non-responders (n = 24), according to their BCR-ABL1 transcription levels after 12 months of imatinib treatment. Genotyping of the CYP2C8*3 and ABCG2 C421A polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while plasma trough concentrations were determined through high-performance liquid chromatography with ultraviolet-diode array detection (HPLC-UV/DAD).

Results: Patients with the CA genotype of ABCG2 C421A showed significantly higher mean plasma trough concentrations of imatinib (CA: 1731 ± 424.7 ng/mL; CC: 1294 ± 381.3 ng/mL; p = 0.0132) and demonstrated a better molecular response compared to those with the CC genotype (p = 0.0395).

Conclusion: The ABCG2 C421A polymorphism significantly influenced imatinib plasma trough concentrations and molecular responses in Egyptian chronic-phase CML patients. Genotyping of this polymorphism in these patients could assist in optimizing imatinib therapy, predicting more favorable treatment outcomes, and enabling the development of more personalized treatment plans.

Keywords: ABCG2; CYP2C8*3; CML; Imatinib.

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Conflict of interest statement

Declarations. Declaration of generative AI and AI-assisted technologies in the writing process: In the preparation of this manuscript, generative AI, specifically OpenAI’s ChatGPT, was utilized to support the writing process. ChatGPT was employed to assist with language refinement, editing, and the restructuring of certain passages to ensure clarity and adherence to scientific writing standards. The use of AI was guided by the authors, who provided all the intellectual content and made final decisions on the presentation and interpretation of the research findings. All AI-generated text was carefully reviewed and edited by the authors to align with the scientific rigor and standards expected of the manuscript. The final content of the manuscript is the result of the authors’ original work and expertise. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Plasma trough concentrations of imatinib in different genotypes of CYP2C8*3 (a) and ABCG2 C421A (b) polymorphisms in CML patients
Fig. 2
Fig. 2
Frequency of different genotypes of CYP2C8*3 (a) and ABCG2 C421A (b) polymorphisms in imatinib responders and non-responders
See this image and copyright information in PMC

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