Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Key Laboratory of Hematology, Nanjing Medical University, Nanjing, China.
Pediatr Blood Cancer. 2023 Oct;70(10):e30545. doi: 10.1002/pbc.30545. Epub 2023 Jul 12.
Dysregulation of microRNAs (miRNAs) targeting genes in the PI3K/Akt pathway has been implicated in the pathogenesis of childhood acute lymphoblastic leukemia (ALL). However, the impact of genetic variants in these miRNAs on ALL susceptibility has not been extensively explored in the Chinese population.
To address this gap, we conducted a case-control study to evaluate the association between genetic variants in five PI3K/AKT pathway-related miRNAs (miR-149, miR-126, miR-492, miR-612, and miR-423) and childhood ALL susceptibility in the Chinese population. Additionally, we investigated the effects of the rs2292832 mutation on ALL cell proliferation and apoptosis.
Our analyses revealed that the miR-149 rs2292832 mutant heterozygous CT genotype was more frequent in the control group than in the ALL cases, indicating a protective effect against ALL (adjusted odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63-0.97, p = .024). Stratification analyses further revealed that the miR-149 rs2292832 CC genotype was associated with an increased risk of childhood ALL in subgroups of older children, females, those with parents who never smoked or drank alcohol, those living in painted houses, those with B-ALL, and those with high-risk ALL. Finally, we observed that the rs2292832 mutation inhibited ALL cell proliferation and induced apoptosis (p = .001), providing a potential mechanism by which this genetic variant may influence ALL susceptibility.
Our study highlights the significant association between the miR-149 rs2292832 genetic variant and childhood ALL susceptibility in the Chinese population. These findings expand our understanding of the complex genetic landscape underlying ALL and have implications for the development of personalized therapeutic strategies.
PI3K/Akt 通路靶向基因的 microRNAs（miRNAs）失调与儿童急性淋巴细胞白血病（ALL）的发病机制有关。然而，这些 miRNA 中的遗传变异对 ALL 易感性的影响在中国人群中尚未得到广泛探讨。
为了解决这一空白，我们进行了病例对照研究，以评估 PI3K/AKT 通路相关的五个 miRNAs（miR-149、miR-126、miR-492、miR-612 和 miR-423）中的遗传变异与中国人群中儿童 ALL 易感性之间的关联。此外，我们还研究了 rs2292832 突变对 ALL 细胞增殖和凋亡的影响。
我们的分析表明，miR-149 rs2292832 突变杂合 CT 基因型在对照组中比 ALL 病例中更为常见，表明其对 ALL 具有保护作用（校正后的优势比 [OR] = 0.78，95%置信区间 [CI] = 0.63-0.97，p = 0.024）。分层分析进一步表明，miR-149 rs2292832 CC 基因型与年龄较大的儿童、女性、父母从不吸烟或饮酒、居住在刷过漆的房屋中的儿童、B-ALL 以及高危 ALL 亚组的儿童 ALL 风险增加相关。最后，我们观察到 rs2292832 突变抑制了 ALL 细胞增殖并诱导了凋亡（p = 0.001），这提供了一种潜在的机制，说明这种遗传变异可能影响 ALL 易感性。
本研究强调了 miR-149 rs2292832 遗传变异与中国人群中儿童 ALL 易感性之间的显著关联。这些发现扩展了我们对 ALL 遗传基础的复杂认识，并对制定个性化治疗策略具有重要意义。
