Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission

Tong Xing, Li-Juan Hu, Hong-Yan Zhao, Chen-Yuan Li, Zhen-Kun Wang, Meng-Zhu Shen, Zhong-Shi Lyu, Jing Wang, Yu Wang, Hao Jiang, Qian Jiang, Ying-Jun Chang, Xiao-Hui Zhang, Yuan Kong () and Xiao-Jun Huang ()
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Tong Xing: Peking University
Li-Juan Hu: Peking University
Hong-Yan Zhao: Peking University
Chen-Yuan Li: Peking University
Zhen-Kun Wang: Peking University
Meng-Zhu Shen: Peking University
Zhong-Shi Lyu: Peking University
Jing Wang: Peking University
Yu Wang: Peking University
Hao Jiang: Peking University
Qian Jiang: Peking University
Ying-Jun Chang: Peking University
Xiao-Hui Zhang: Peking University
Yuan Kong: Peking University
Xiao-Jun Huang: Peking University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Although acute myeloid leukemia (AML) affects hematopoietic stem cell (HSC)-supportive microenvironment, it is largely unknown whether leukemia-modified bone marrow (BM) microenvironment can be remodeled to support normal hematopoiesis after complete remission (CR). As a key element of BM microenvironment, endothelial progenitor cells (EPCs) provide a feasible way to investigate BM microenvironment remodeling. Here, we find reduced and dysfunctional BM EPCs in AML patients, characterized by impaired angiogenesis and high ROS levels, could be partially remodeled after CR and improved by N-acetyl-L-cysteine (NAC). Importantly, HSC-supporting ability of BM EPCs is partially recovered, whereas leukemia-supporting ability is decreased in CR patients. Mechanistically, the transcriptome characteristics of leukemia-modified BM EPCs return to near-normal after CR. In a classic AML mouse and chemotherapy model, BM vasculature and normal hematopoiesis are reversed after CR. In summary, we provide further insights into how leukemia-modified BM microenvironment can be remodeled to support normal hematopoiesis after CR, which can be further improved by NAC.

Date: 2024
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DOI: 10.1038/s41467-024-55051-x

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