Szymczyk Agnieszka, Chocholska Sylwia, Radko Katarzyna, Hus Marek, Podhorecka Monika
Department of Hematology, National Medical Institute of the Ministry of Interior and Administration, Warsaw, Poland.
Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland.
PLoS One. 2025 Jun 24;20(6):e0324320. doi: 10.1371/journal.pone.0324320. eCollection 2025.
Acute myeloid leukemia (AML) is associated with the accumulation of acquired genetic disorders. Moreorver chromosomal and molecular changes are independent prognostic factors that are taken into account to determine prognosis and treatment. MicroRNAs are novel gene regulators, which have been recognized to play an important role in pathological leukemogenesis. This study is aimed to analyze the possible role of micro RNAs as a markers predicting the outcome to induction chemotherapy based on cytarabine.
The expression of miR-34a, miR-191, miR-199a and miR-199b in previously separated bone marrow cells was assessed at the moment of diagnosis in 44 AML patients with use of qRQ-PCR technique. Assessment of response to induction therapy was based on criteria for response to treatment proposed by European LeukemiaNet (ELN).
Only the expression level of miR-191a out of all analyzed microRNAs was significantly associated with the induction chemotherapy response. We detected also significantly higher expression of miR-191 in FLT3-ITD negative group in comparison to FLT3-ITD positive subjects. For miR-34a, miR-199a and miR-199b, no relationship was found between their expression and FLT3-ITD, NPM1 and CEBPA mutations. It was also shown that in the group of patients with low miR-191 expression, the number of myeloblasts was higher (p < 0.05).
These results may prove an important role of miR-191a expression as a predictor of response to the induction chemotherapy based on cytarabine, even in cases when other risk factors are absent.
急性髓系白血病(AML)与获得性遗传疾病的积累有关。此外,染色体和分子变化是独立的预后因素,在确定预后和治疗时会被考虑在内。微小RNA是新型基因调节因子,已被认为在白血病病理发生过程中起重要作用。本研究旨在分析微小RNA作为基于阿糖胞苷的诱导化疗预后预测标志物的可能作用。
使用qRQ-PCR技术,在44例AML患者诊断时评估先前分离的骨髓细胞中miR-34a、miR-191、miR-199a和miR-199b的表达。根据欧洲白血病网络(ELN)提出的治疗反应标准评估诱导治疗反应。
在所有分析的微小RNA中,只有miR-191a的表达水平与诱导化疗反应显著相关。我们还检测到,与FLT3-ITD阳性受试者相比,FLT3-ITD阴性组中miR-191的表达明显更高。对于miR-34a、miR-199a和miR-199b,未发现它们的表达与FLT3-ITD、NPM1和CEBPA突变之间存在关联。还表明,在miR-191表达低的患者组中,成髓细胞数量更高(p < 0.05)。
这些结果可能证明miR-191a表达作为基于阿糖胞苷的诱导化疗反应预测指标具有重要作用,即使在没有其他风险因素的情况下也是如此。