ADAR1 polymorphisms contribute to increased susceptibility in pediatric acute lymphoblastic leukemia.
Ann Hematol
; 102(9): 2483-2492, 2023 Sep.
Article
em En
| MEDLINE
| ID: mdl-37217676
ABSTRACT
Adenosine deaminase acting on RNA1 (ADAR1), catalyzing post-transcriptional adenosine-to-inosine RNA editing, promotes cancer progression and therapeutic resistance. However, very little is known about the association of ADAR1 variants with acute lymphoblastic leukemia (ALL). Here we first explored the potential association of three polymorphisms (rs9616, rs2229857, and rs1127313) of ADAR1 with susceptibility in Chinese children ALL, then functionally characterized ADAR1 in ALL. Our results demonstrated that rs9616 T and rs2229857 T were associated with increased expression of ADAR1 mRNA and higher risk to ALL. Of note, a stronger risk effect of rs2229857 T genotypes was found among relapse children. Furthermore, ADAR1 knockdown specifically inhibited proliferation and promoted apoptosis in ALL cells. These findings give insights into a mechanism by which the risk variant at rs9616 and rs2229857 modulate ADAR1 expression and confers a predisposition and relapse risk to ALL, and representing a potential novel biomarker for pediatric ALL.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Adenosina Desaminase
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article