Acute myeloid leukemia cells induce senescence and adipogenic differentiation of mesenchymal stem cells in a tumor-supportive microenvironment at the same time

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-09-15 DOI:10.1016/j.cellsig.2025.112136

Yanju Li , Chike Zhang , Yan Zhang , Yi Huang , Xiaoshuang Yuan , Bo Yang , Zhixu He , Yang Liu , Feiqing Wang

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Abstract

Acute myeloid leukemia (AML) actively induces the transformation of a normal hematopoietic niche into a tumor-supportive microenvironment. Among them, Mesenchymal stem cells (MSCs)are closely associated with the genesis and development of AML. MSCs derived from AML patients (AML-MSC) show a senescent state, with possibly biased differentiation ability. However, it remains unclear whether AML-MSC exhibits the dual pathological evolution of both senescence characteristics and lipogenic differentiation bias in the microenvironment at the same time. Thus, this study, by analyzing AML-MSC and MSC co-cultured with tumor cells over a long period， revealed that AML affects the AMPK/SIRT1 signaling pathway, inducing an increase in reactive oxygen species in the microenvironment of MSCs, thereby leading to significantly altered metabolic processes, adipose-biased differentiation capacity, and senescence of MSCs. These findings clarify the mechanism by which AML cells actively contribute to the evolution of the tumor microenvironment, providing a theoretical basis for future dual targeting of supportive ecological niches.

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急性髓系白血病细胞在肿瘤支持微环境中诱导间充质干细胞衰老和成脂分化。

急性髓性白血病（AML）积极诱导正常造血生态位转化为肿瘤支持微环境。其中，间充质干细胞（Mesenchymal stem cells, MSCs）与AML的发生发展密切相关。来源于AML患者的间充质干细胞（AML- msc）表现出衰老状态，可能具有偏分化能力。然而，AML-MSC是否在微环境中同时表现出衰老特征和脂质分化偏向的双重病理进化尚不清楚。因此，本研究通过分析AML-MSC和长期与肿瘤细胞共培养的MSC，发现AML影响AMPK/SIRT1信号通路，诱导MSCs微环境中活性氧的增加，从而导致MSCs代谢过程、脂肪偏向分化能力和衰老的显著改变。这些发现阐明了AML细胞积极参与肿瘤微环境进化的机制，为未来双靶向支持性生态位提供了理论基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.