Kuhestani-Dehaghi Bentolhoda, Amirpour Mozhgan, Nabigol Maryam, Keshavarz Ali, Vazifeh Shiran Nader, Rahmani-Seraji Hamideh, Dehghani-Ghorbi Mahmoud, Allahbakhshian Farsani Mehdi
Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box 15468-15514, Tehran, Iran.
Department of Hematology and Oncology, Taleghani Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran.
Mol Biol Rep. 2024 Dec 18;52(1):62. doi: 10.1007/s11033-024-10155-x.
The progression of leukemia is substantially associated with the interactions of leukemic cells with surrounding cells within the bone marrow microenvironment (BMM), and these interactions were facilitated using exosomes as vital mediators. The current study aimed to examine the proliferative effects of exosomes derived from the HL-60 cell line, a representative of acute myeloblastic leukemia (AML), on the cell cycle progression of human bone marrow mesenchymal stromal cells (hBM-MSCs), a key element of the BMM.
hBM-MSCs were treated with different concentrations of AML-derived exosomes from the HL-60 cell line. The results were obtained from MTT, cell proliferation, cell cycle, and RT-qPCR evaluations. In the current study, we found that the proliferation effects of AML-derived exosomes relied on the dose and the time, and the optimal effects of exosomes were seen in 50 μg/ml, 48 h treatment. Flow cytometry analysis revealed a significant increase in the G1 phase, showing a 1.6-fold change compared to the control group (p value < 0.0001). RT-qPCR results demonstrated a significant upregulation of CCND1 (3.3-fold, p value < 0.0001), CDK4 (3.7-fold, p value < 0.0001), CDK6 (3.3-fold, p value < 0.0001), RAS (3.2-fold, p value < 0.0001), and Erk (3.4-fold, p value < 0.0001) expression levels, along with increased Ki-67 (2.6-fold, p value < 0.0001) levels. Moreover, treatment with 50 μg/ml, 48 h of AML-derived exosomes resulted in a notable reduction in BM-MSC apoptosis both in early (p value < 0.0001) and late (p value < 0.0001) apoptosis rate compared to control group.
The findings will be of interest to AML-derived exosomes, which were able to potentiate the activation of the signaling pathways involved in the survival and proliferation of hBM-MSCs. Our findings suggest their specific targeting as a potential therapeutic strategy against cancer progression and metastasis.
白血病的进展与白血病细胞与骨髓微环境（BMM）中周围细胞的相互作用密切相关，而外泌体作为重要介质促进了这些相互作用。本研究旨在检测源自急性髓性白血病（AML）代表性细胞系HL-60的外泌体对人骨髓间充质基质细胞（hBM-MSCs）细胞周期进程的增殖作用，hBM-MSCs是BMM的关键组成部分。
用不同浓度源自HL-60细胞系的AML外泌体处理hBM-MSCs。通过MTT、细胞增殖、细胞周期和RT-qPCR评估获得结果。在本研究中，我们发现AML外泌体的增殖作用依赖于剂量和时间，外泌体在50μg/ml、处理48小时时效果最佳。流式细胞术分析显示G1期显著增加，与对照组相比变化了1.6倍（p值<0.0001）。RT-qPCR结果表明CCND1（3.3倍，p值<0.0001）、CDK4（3.7倍，p值<0.0001）、CDK6（3.3倍，p值<0.0001）、RAS（3.2倍，p值<0.0001）和Erk（3.4倍，p值<0.0001）的表达水平显著上调，同时Ki-67水平升高（2.6倍，p值<0.0001）。此外，与对照组相比，用50μg/ml、处理48小时的AML外泌体处理导致BM-MSC早期（p值<0.0001）和晚期（p值<0.0001）凋亡率显著降低。
AML来源的外泌体能够增强参与hBM-MSCs存活和增殖的信号通路的激活，这些发现将引起人们的兴趣。我们的研究结果表明将其作为针对癌症进展和转移的潜在治疗策略进行特异性靶向治疗。
