Laboratory of Experimental Hematology, Department of Haematology, Jules Bordet Institute, Université Libre de Bruxelles, 1000 Brussels, Belgium.
Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), Department of Medicine, University of Montreal, Montreal, QC H2X 0A9, Canada.
Int J Mol Sci. 2020 Sep 25;21(19):7065. doi: 10.3390/ijms21197065.
In addition to their roles in different biological processes, microRNAs in the tumor microenvironment appear to be potential diagnostic and prognostic biomarkers for various malignant diseases, including acute myeloid leukemia (AML). To date, no screening of circulating miRNAs has been carried out in the bone marrow compartment of AML. Accordingly, we investigated the circulating miRNA profile in AML bone marrow at diagnosis (AMLD) and first complete remission post treatment (AMLPT) in comparison to healthy donors (HD).
Circulating miRNAs were isolated from AML bone marrow aspirations, and a low-density TaqMan miRNA array was performed to identify deregulated miRNAs followed by quantitative RT-PCR to validate the results. Bioinformatic analysis was conducted to evaluate the diagnostic and prognostic accuracy of the highly and significantly identified deregulated miRNA(s) as potential candidate biomarker(s).
We found several deregulated miRNAs between the AMLD vs. HD vs. AMLPT groups, which were involved in tumor progression and immune suppression pathways. We also identified significant diagnostic and prognostic signatures with the ability to predict AML patient treatment response.
This study provides a possible role of enriched circulating bone marrow miRNAs in the initiation and progression of AML and highlights new markers for prognosis and treatment monitoring.
除了在不同的生物学过程中发挥作用外，肿瘤微环境中的 microRNAs 似乎是各种恶性疾病（包括急性髓系白血病 [AML]）的潜在诊断和预后生物标志物。迄今为止，尚未对 AML 的骨髓腔中循环的 microRNAs 进行筛选。因此，我们在 AML 诊断时的骨髓（AMLD）和首次完全缓解后的骨髓（AMLPT）与健康供体（HD）进行了比较，研究了循环 microRNA 谱。
从 AML 骨髓抽吸物中分离循环 microRNAs，并进行低密度 TaqMan microRNA 阵列分析以鉴定失调的 microRNAs，然后进行定量 RT-PCR 以验证结果。进行生物信息学分析，以评估高度和显著鉴定的失调 microRNA 作为潜在候选生物标志物的诊断和预后准确性。
我们在 AMLD 与 HD 与 AMLPT 组之间发现了几种失调的 microRNAs，这些 microRNAs涉及肿瘤进展和免疫抑制途径。我们还确定了具有预测 AML 患者治疗反应能力的显著诊断和预后特征。
这项研究提供了富含循环骨髓 microRNAs 在 AML 起始和进展中的可能作用，并强调了预后和治疗监测的新标志物。
