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Impact of Variants in the ATIC and ARID5B Genes on Therapeutic Failure with Imatinib in Patients with Chronic Myeloid Leukemia

Authors :
Karla Beatriz Cardias Cereja Pantoja
Tereza Cristina de Brito Azevedo
Darlen Cardoso de Carvalho
Natasha Monte
Amanda de Nazaré Cohen Paes
Maria Clara da Costa Barros
Lui Wallacy Morikawa Souza Vinagre
Ana Rosa Sales de Freitas
Rommel Mario Rodríguez Burbano
Paulo Pimentel de Assumpção
Sidney Emanuel Batista dos Santos
Marianne Rodrigues Fernandes
Ney Pereira Carneiro dos Santos
Source :
Genes; Volume 13; Issue 2; Pages: 330
Publication Year :
2022
Publisher :
Multidisciplinary Digital Publishing Institute, 2022.

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm derived from the balanced reciprocal translocation of chromosomes 9 and 22 t (9q34 and 22q11), which leads to the formation of the Philadelphia chromosome and fusion of the BCR-ABL genes. The first-line treatment for CML is imatinib, a tyrosine kinase inhibitor that acts on the BCR-ABL protein. However, even though it is a target-specific drug, about 25% of patients do not respond to this treatment. The resistance mechanisms involved in this process have been investigated and studies have shown that germinal alterations can influence this mechanism. The aim of this work was to investigate 32 polymorphisms in 24 genes of carcinogenic pathway to verify the influence of these genetic variants on the response to treatment with imatinib. Our results demonstrated that individuals with the recessive GG genotype for the rs2372536 variant in the ATIC gene are approximately three times more likely to experience treatment failure with imatinib (p = 0.045, HR = 2.726, 95% CI = 0.9986–7.441), as well as individuals with the TT genotype for the rs10821936 variant in the ARID5B gene, who also have a higher risk for treatment failure with imatinib over time (p = 0.02, HR = 0.4053, IC 95% = 0.1802–0.911). In conclusion, we show that variants in the ATIC and ARIDB5 gene, never screened in previous studies, could potentially influence the therapeutic response to imatinib in patients treated for CML.

Details

Language :
English
ISSN :
20734425
Database :
OpenAIRE
Journal :
Genes; Volume 13; Issue 2; Pages: 330
Accession number :
edsair.doi.dedup.....8f6e17f752801dcba4a524c2e52c4fe6
Full Text :
https://doi.org/10.3390/genes13020330