Functional genetic variants in ATG10 are associated with acute myeloid leukemia

• Autor(a) principal: Castro, Isabel
• Data de Publicação: 2021
• 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
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/72917
• topic: Acute myeloid leukemia; ATG10; Autophagy; Single nucleotide polymorphism; Science & Technology

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>_rs1864182G 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>_rs3734114C 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>_rs1864182G 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.