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https://hdl.handle.net/1822/72917
Título: | Functional genetic variants in ATG10 are associated with acute myeloid leukemia |
Autor(es): | Castro, Isabel Marques, Maria Belém Sousa Sampaio Areias, Anabela Cepa Sousa, Hugo Fernandes, Ângela Sanchez-Maldonado, José Manuel Cunha, Cristina Amorim Carvalho, Agostinho Sainz, Juan Ludovico, Paula |
Palavras-chave: | Acute myeloid leukemia ATG10 Autophagy Single nucleotide polymorphism |
Data: | 16-Mar-2021 |
Editora: | Multidisciplinary Digital Publishing Institute (MDPI) |
Revista: | Cancers |
Citação: | Castro, I.; Sampaio-Marques, B.; C. Areias, A.; Sousa, H.; Fernandes, Â.; Sanchez-Maldonado, J.M.; Cunha, C.; Carvalho, A.; Sainz, J.; Ludovico, P. Functional Genetic Variants in ATG10 Are Associated with Acute Myeloid Leukemia. Cancers 2021, 13, 1344. https://doi.org/10.3390/cancers13061344 |
Resumo(s): | Acute myeloid leukemia (AML) is the most common acute leukemia, characterized by a heterogeneous genetic landscape contributing, among others, to the occurrence of metabolic reprogramming. Autophagy, a key player on metabolism, plays an essential role in AML. Here, we examined the association of three potentially functional genetic polymorphisms in the <i>ATG10</i> gene, central for the autophagosome formation. We screened a multicenter cohort involving 309 AML patients and 356 healthy subjects for three <i>ATG10</i> SNPs: rs1864182T>G, rs1864183C>T and rs3734114T>C. The functional consequences of the <i>ATG10</i> SNPs in its canonical function were investigated in vitro using peripheral blood mononuclear cells from a cohort of 46 healthy individuals. Logistic regression analysis adjusted for age and gender revealed that patients carrying the <i>ATG10</i><sub>rs1864182G</sub> allele showed a significantly decreased risk of developing AML (OR [odds ratio] = 0.58, <i>p</i> = 0.001), whereas patients carrying the homozygous <i>ATG10</i><sub>rs3734114C</sub> allele had a significantly increased risk of developing AML (OR = 2.70, <i>p</i> = 0.004). Functional analysis showed that individuals carrying the <i>ATG10</i><sub>rs1864182G</sub> allele had decreased autophagy when compared to homozygous major allele carriers. Our results uncover the potential of screening for <i>ATG10</i> genetic variants in AML prevention strategies, in particular for subjects carrying other AML risk factors such as elderly individuals with clonal hematopoiesis of indeterminate potential. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/72917 |
DOI: | 10.3390/cancers13061344 |
e-ISSN: | 2072-6694 |
Versão da editora: | https://www.mdpi.com/2072-6694/13/6/1344 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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cancers-13-01344-v3.pdf | 2,1 MB | Adobe PDF | Ver/Abrir |
Este trabalho está licenciado sob uma Licença Creative Commons