Department of Hematology/Oncology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, 9 Jinsui Road, Zhujiang Newtown, Tianhe District, Guangzhou, 510623, Guangdong, China.
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, China.
Ann Hematol. 2023 Sep;102(9):2483-2492. doi: 10.1007/s00277-023-05285-4. Epub 2023 May 22.
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.
RNA1 腺苷脱氨酶（ADAR1）作用，催化转录后腺苷到肌苷 RNA 编辑，促进癌症的进展和治疗耐药性。然而，对于 ADAR1 变体与急性淋巴细胞白血病（ALL）之间的关联知之甚少。在这里，我们首先探讨了 ADAR1 的三个多态性（rs9616、rs2229857 和 rs1127313）与中国儿童 ALL 易感性的潜在关联，然后对 ALL 中的 ADAR1 进行了功能表征。我们的结果表明，rs9616T 和 rs2229857T 与 ADAR1mRNA 的表达增加和 ALL 风险增加相关。值得注意的是，rs2229857T 基因型在复发儿童中具有更强的风险效应。此外，ADAR1 敲低特异性抑制 ALL 细胞的增殖并促进凋亡。这些发现为 rs9616 和 rs2229857 风险变体调节 ADAR1 表达并赋予 ALL 易感性和复发风险的机制提供了深入了解，并代表了儿科 ALL 的潜在新型生物标志物。
