{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:55:03Z","timestamp":1764784503498,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T00:00:00Z","timestamp":1600992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["BRL 48,000"],"award-info":[{"award-number":["BRL 48,000"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Acute lymphoblastic leukemia (ALL) is the leading cause of death from pediatric cancer worldwide. However, marked ethnic disparities are found in the treatment of childhood ALL with less effective results and higher mortality rates being obtained in populations with a high level of Native American ancestry. Genetic variations of the patient can affect resistance to ALL chemotherapy and potentially play an important role in this disparity. In the present study, we investigated the association of 16 genetic polymorphisms with the cell and metabolic pathways of the chemotherapeutic agents used in the treatment of ALL with the risk of death in treating childhood ALL in patients with a high contribution of Amerindian ancestry, coming from the Brazilian Amazon. The study included 121 patients with B-cell ALL treated with the BFM-2002 protocol. We are the first to identify the association between the TPMT gene rs1142345 polymorphism and the high risk of death in treating childhood ALL. Patients with the CC genotype had an approximately 25.5 times higher risk of dying during treatment of the disease than patients with other genotypes (p = 0.019). These results may help elucidate how the patient\u2019s genetic characteristics contribute to the mortality disparity in populations with a high contribution of Native American ancestry. The rs1142345 variant of the TPMT gene could be used as a potential marker to early stratify patients at high risk of death in treating childhood ALL in the investigated population.<\/jats:p>","DOI":"10.3390\/genes11101132","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T08:02:58Z","timestamp":1601280178000},"page":"1132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Association between the TPMT*3C (rs1142345) Polymorphism and the Risk of Death in the Treatment of Acute Lymphoblastic Leukemia in Children from the Brazilian Amazon Region"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2716-860X","authenticated-orcid":false,"given":"Darlen","family":"Cardoso de Carvalho","sequence":"first","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana","family":"Pereira Colares Leit\u00e3o","sequence":"additional","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Augusto Rodrigues","family":"Mello Junior","sequence":"additional","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alayde","family":"Vieira Wanderley","sequence":"additional","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"},{"name":"Departamento de Pediatria, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiane Piedade de","family":"Souza","sequence":"additional","affiliation":[{"name":"Human and Medical Genetics Laboratory, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal do Par\u00e1, Bel\u00e9m 66075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Borges Andrade de S\u00e1","sequence":"additional","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Cohen-Paes","sequence":"additional","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1396-3442","authenticated-orcid":false,"given":"Marianne","family":"Rodrigues Fernandes","sequence":"additional","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidney","family":"Santos","sequence":"additional","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"},{"name":"Human and Medical Genetics Laboratory, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal do Par\u00e1, Bel\u00e9m 66075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Salim Khayat","sequence":"additional","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo","family":"Pimentel de Assump\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"},{"name":"Jo\u00e3o de Barros Barreto University Hospital, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ney","family":"Pereira Carneiro dos Santos","sequence":"additional","affiliation":[{"name":"Oncology Research Nucleus, Universidade Federal do Par\u00e1, Bel\u00e9m 66063-023, Brazil"},{"name":"Human and Medical Genetics Laboratory, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal do Par\u00e1, Bel\u00e9m 66075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1200\/JCO.2010.30.7405","article-title":"Biology, Risk Stratification, and Therapy of Pediatric Acute Leukemias: An Update","volume":"29","author":"Pui","year":"2011","journal-title":"J. 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