RT Journal Article
T1 Functional Genetic Variants in ATG10 Are Associated with Acute Myeloid Leukemia.
A1 Castro, Isabel
A1 Sampaio-Marques, Belém
A1 C Areias, Anabela
A1 Sousa, Hugo
A1 Fernandes, Ângela
A1 Sanchez-Maldonado, José Manuel
A1 Cunha, Cristina
A1 Carvalho, Agostinho
A1 Sainz, Juan
A1 Ludovico, Paula
K1 ATG10
K1 acute myeloid leukemia
K1 autophagy
K1 single nucleotide polymorphism
AB 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 ATG10 gene, central for the autophagosome formation. We screened a multicenter cohort involving 309 AML patients and 356 healthy subjects for three ATG10 SNPs: rs1864182T>G, rs1864183C>T and rs3734114T>C. The functional consequences of the ATG10 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 ATG10rs1864182G allele showed a significantly decreased risk of developing AML (OR [odds ratio] = 0.58, p = 0.001), whereas patients carrying the homozygous ATG10rs3734114C allele had a significantly increased risk of developing AML (OR = 2.70, p = 0.004). Functional analysis showed that individuals carrying the ATG10rs1864182G allele had decreased autophagy when compared to homozygous major allele carriers. Our results uncover the potential of screening for ATG10 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.
SN 2072-6694
YR 2021
FD 2021-03-16
LK https://hdl.handle.net/10668/28432
UL https://hdl.handle.net/10668/28432
LA en
DS RISalud
RD Apr 19, 2025