| 摘要: |
| 目的:探讨儿童急性髓系白血病(AML)患儿骨髓(BM)miR-497-5p 表达与中国儿童白血病协作组(CCLG)-AML 2015 方
案诱导化疗反应的相关性,并分析其潜在靶基因及信号通路。方法:前瞻性纳入南充市中心医院2022 年3 月至2024 年3 月收
治的58 例5~14 岁初诊AML 患儿,均接受CCLG-AML 2015 诱导方案,评估2 个疗程的治疗反应,将获得完全缓解(CR)的患儿
纳入CR 组,其他患儿纳入非CR 组。通过逆转录定量聚合酶链反应检测BM miR-497-5p 水平,酶联免疫吸附试验测定试剂盒检
测血清白细胞介素(IL)-1β、IL-6 和肿瘤坏死因子(TNF)-α、转化生长因子(TGF)-β1 水平。生物信息学预测靶基因及通路。结
果:29 例(50%)达到CR。CR 组BM miR-497-5p 水平高于非CR 组(Z =-4. 324,P<0. 01)。预测AML 患儿诱导化疗反应的曲线
下面积为0. 831(95%CI 0. 723~0. 938),最佳截断值为0. 44。以该值分组,低miR-497-5p 亚组高危患儿比例以及白细胞计数相
对更高(P<0. 05)。经Firth 惩罚logistic 回归分析,BM miR-497-5p 相对表达水平≥0. 44 为诱导化疗反应的独立保护因素(OR=
0. 038,95%CI 0. 006~0. 237,P<0. 001)。BM miR-497-5p 与TNF-α(ρ =-0. 318,P = 0. 015)、TGF-β1(ρ =-0. 430,P<0. 001)、IL-6
(ρ =-0. 395,P =0. 002)和IL-1β(ρ =-0. 273,P =0. 038) 均呈负相关。生物信息学分析显示,miR-497-5p 靶基因多富集于Wnt、
TGF-β、p53 等通路。结论:BM miR-497-5p 表达水平降低与儿童AML 患者CCLG-AML 2015 诱导化疗反应不足有关,表明其可
能成为儿童AML 的预后生物标志物。其潜在靶基因及信号通路仅为生信预测,分子机制尚待后续功能实验验证。 |
| 关键词: 急性髓系白血病 儿童 CCLG-AML 2015 诱导化疗方案 治疗反应 miR-497-5p |
| DOI：doi:10.13407/j.cnki.jpp.1672-108X.2026.10.009 |
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| 基金项目: |
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| Correlation and Predictive Significance of Bone Marrow miR-497-5p with the Response to InductionChemotherapy of CCLG-AML 2015 Regimen in Children with Acute Myeloid Leukemia |
| Sun Yi1, Zhang Juan1, Bai Jing1, Zhuge Ruonan2 |
| ((1. Nanchong Hospital, Beijing Anzhen Hospital, Capital Medica1 University, Nanchong Central Hospital, Sichuan Nanchong 637000, China; 2. Women’s and Children’s Hospital of Ningbo University, Zhekiang Ningbo 725000, China)) |
| Abstract: |
| Objective: To probe into the correlation between expression of miR-497-5p in the bone marrow (BM) of children with acute
myeloid leukemia (AML) and the response to induction chemotherapy with Chinese Children’s Leukemia Group (CCLG)-AML 2015
regimen, and to analyze its potential target genes and signaling pathways. Methods: A total of 58 children aged from 5 to 14 years who
were newly diagnosed with AML and admitted into Nanchong Central Hospital from Mar. 2022 to Mar. 2024 were prospectively enrolled.
All of them received the CCLG-AML 2015 induction regimen, and treatment responses were evaluated after two cycles. Patients were
divided into the complete remission (CR) group and non-CR group. BM miR-497-5p was detected by reverse transcription quantitative
polymerase chain reaction, and the levels of serum interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and transforming growth
factor (TGF)-β1 were detected by enzyme-linked immunosorbent assay. Bioinformatic analysis was performed to predict target genes and
signaling pathways. Results: The overall CR rate was 50. 00% (29/ 58). BM miR-497-5p in CR group was significantly higher than that
in non-CR group (Z =-4. 324, P<0. 01). The area under the curve of the BM miR-497-5p for predicting the response to induction
chemotherapy in children with AML was 0. 831 (95%CI 0. 723 to 0. 938), and the optimal cut-off value was 0. 44. The proportion of
high-risk children and the white blood cell count in the low miR-497-5p subgroup were relatively higher (P<0. 05). Firth penalized
logistic regression analysis revealed that relative expression level of BM miR-497-5p⩾0. 44 was an independent protective factor for
response to induction chemotherapy (OR=0. 038, 95%CI 0. 006 to 0. 237, P<0. 001). BM miR-497-5p relative expression level was
negatively correlated with the serum levels of TNF-α (ρ =-0. 318, P =0. 015), TGF-β1 (ρ =-0. 430, P<0. 001), IL-6 (ρ =-0. 395,
P = 0. 002), and IL-1β (ρ = -0. 273, P = 0. 038). Bioinformatic enrichment indicated that miR-497-5p target genes were mainly
enriched in Wnt, TGF-β, and p53 signaling pathways. Conclusion: The decreased expression level of BM miR-497-5p is associated
with insufficient response to CCLG-AML 2015 induction chemotherapy in children with AML, indicating that it may become a prognostic
biomarker for AML. Potential target genes and pathways are merely bioinformatic predictions, and further functional experiments are
required to clarify the underlying mechanism. |
| Key words: acute myeloid leukemia children CCLG-AML 2015 induction chemotherapy regimen treatment response miR-497-5p |
