Publicação
Functional genetic variants in ATG10 are associated with acute myeloid leukemia
| Resumo: | 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. |
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| Autores principais: | Castro, Isabel |
| Outros Autores: | 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 |
| Assunto: | Acute myeloid leukemia ATG10 Autophagy Single nucleotide polymorphism |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | 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. |
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