Acute lymphoblastic leukemia (ALL) is one of the most frequent hematological malignancies in children, representing approximately 25 % of all pediatric cancers. Despite striking advances in ALL treatments, a small population of patients does not still respond to chemotherapy, raising the number of deaths in children. ABC transporters are one of the major causes of multidrug resistance (MDR) in cancers and overexpression of ABCA3 is directly associated with increased chemo-resistance in pediatric ALL. Here, we aimed to identify the microRNAs (miRNAs) which may regulate the expression of ABCA3 in childhood ALL. Bone marrow samples from a total of 50 ALLs and 59 controls were collected and after in silico and literature search, miR-324-3p and miR-508-5p were nominated from a list of putative miRNAs targeting ABCA3. Our qPCR analysis showed a low expression profile of selected miRNAs in pediatric ALL patients compared with non-cancer controls. Furthermore, we found that both miR-324-3p and miR-508-5p were significantly differentially expressed between patients with positive and negative minimal residual disease (MRD + vs MRD-) after one year of chemotherapy while only miR-508-5p was underexpressed in relapsed ALL patients. Additionally, a negative correlation was identified between the expression of these two miRNAs and ABCA3, supporting the regulatory effect of them on drug resistance through interacting with ABCA3. Overall, we suggested miR-324-3p and miR-508-5p as potential diagnostic and drug-resistant biomarkers in pediatric ALL. Moreover, our findings presented miR-508-5p to behave as a promising relapsed indicator in childhood ALL which can be applied in the development of novel therapeutic strategies.

急性淋巴细胞白血病 (ALL) 是儿童最常见的血液系统恶性肿瘤之一，约占所有儿科癌症的 25%。尽管 ALL 治疗取得了显着进展，但仍有一小部分患者对化疗没有反应，从而增加了儿童死亡人数。ABC 转运蛋白是癌症中多药耐药 (MDR) 的主要原因之一，ABCA3 的过度表达与儿科 ALL 的化学耐药性增加直接相关。在这里，我们旨在鉴定可能调节儿童 ALL中ABCA3表达的 microRNA (miRNA) 。收集了总共 50 名 ALL 和 59 名对照的骨髓样本，并进行了计算机模拟和文献检索，miR-324-3p 和 miR-508-5p 是从靶向ABCA3的推定 miRNA 列表中提名的。我们的 qPCR 分析显示，与非癌症对照相比，儿科 ALL 患者所选 miRNA 的表达谱较低。此外，我们发现在化疗一年后，miR-324-3p 和 miR-508-5p 在微小残留病阳性和阴性（MRD + vs MRD-）患者之间均有显着差异表达，而只有 miR-508-5p在复发性 ALL 患者中表达不足。此外，发现这两种 miRNA 的表达与ABCA3呈负相关，支持它们通过与ABCA3相互作用对耐药性的调节作用. 总体而言，我们建议 miR-324-3p 和 miR-508-5p 作为儿童 ALL 的潜在诊断和耐药生物标志物。此外，我们的研究结果表明 miR-508-5p 可作为儿童 ALL 的有希望的复发指标，可用于开发新的治疗策略。