{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T19:21:34Z","timestamp":1781378494277,"version":"3.54.1"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["Chamada Universal- MCTI \/ CNPq No. 14\/2013"],"award-info":[{"award-number":["Chamada Universal- MCTI \/ CNPq No. 14\/2013"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007382","name":"Federal University of Para","doi-asserted-by":"publisher","award":["EDITAL 06\/2021 \u2013  PROGRAMA DE APOIO \u00c0 PUBLICA\u00c7\u00c3O QUALIFICADA - PAPQ\/ Pr\u00f3-Reitoria de Pesquisa e P\u00f3s-Gradua\u00e7\u00e3o (PROPESP)"],"award-info":[{"award-number":["EDITAL 06\/2021 \u2013  PROGRAMA DE APOIO \u00c0 PUBLICA\u00c7\u00c3O QUALIFICADA - PAPQ\/ Pr\u00f3-Reitoria de Pesquisa e P\u00f3s-Gradua\u00e7\u00e3o (PROPESP)"]}],"id":[{"id":"10.13039\/501100007382","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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\u20137.441), 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\u20130.911). 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.<\/jats:p>","DOI":"10.3390\/genes13020330","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T02:37:46Z","timestamp":1644547066000},"page":"330","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impact of Variants in the ATIC and ARID5B Genes on Therapeutic Failure with Imatinib in Patients with Chronic Myeloid Leukemia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-3722","authenticated-orcid":false,"given":"Karla Beatriz Cardias","family":"Cereja Pantoja","sequence":"first","affiliation":[{"name":"N\u00facleo de Pesquisas em Oncologia, Universidade Federal do Par\u00e1, Bel\u00e9m 66073-005, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9352-326X","authenticated-orcid":false,"given":"Tereza Cristina de Brito","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Hospital Ophir Loyola, Bel\u00e9m 66063-240, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2716-860X","authenticated-orcid":false,"given":"Darlen Cardoso de","family":"Carvalho","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Oncologia, Universidade Federal do Par\u00e1, Bel\u00e9m 66073-005, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4061-5045","authenticated-orcid":false,"given":"Natasha","family":"Monte","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Oncologia, Universidade Federal do Par\u00e1, Bel\u00e9m 66073-005, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3548-292X","authenticated-orcid":false,"given":"Amanda de Nazar\u00e9","family":"Cohen Paes","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Oncologia, Universidade Federal do Par\u00e1, Bel\u00e9m 66073-005, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5886-4069","authenticated-orcid":false,"given":"Maria Clara da Costa","family":"Barros","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica Humana e M\u00e9dica, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal do Par\u00e1, Bel\u00e9m 66077-830, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7063-6149","authenticated-orcid":false,"given":"Lui Wallacy Morikawa Souza","family":"Vinagre","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Oncologia, Universidade Federal do Par\u00e1, Bel\u00e9m 66073-005, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Rosa Sales de","family":"Freitas","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Oncologia, Universidade Federal do Par\u00e1, Bel\u00e9m 66073-005, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-234X","authenticated-orcid":false,"given":"Rommel Mario Rodr\u00edguez","family":"Burbano","sequence":"additional","affiliation":[{"name":"Hospital Ophir Loyola, Bel\u00e9m 66063-240, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3846-8445","authenticated-orcid":false,"given":"Paulo Pimentel de","family":"Assump\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Oncologia, Universidade Federal do Par\u00e1, Bel\u00e9m 66073-005, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8622-9417","authenticated-orcid":false,"given":"Sidney Emanuel Batista dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica Humana e M\u00e9dica, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal do Par\u00e1, Bel\u00e9m 66077-830, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1396-3442","authenticated-orcid":false,"given":"Marianne Rodrigues","family":"Fernandes","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Oncologia, Universidade Federal do Par\u00e1, Bel\u00e9m 66073-005, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-7037","authenticated-orcid":false,"given":"Ney Pereira 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