Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission
Tong Xing, Lijuan Hu, Hongyan Zhao, Chenyuan Li, Zhenkun Wang, Meng-Zhu Shen, Zhong‐Shi Lyu, Jing Wang, Yu Wang, Hao Jiang, Qian Jiang, Ying‐Jun Chang, Xiaohui Zhang, Yuan Kong, Xiao‐Jun Huang
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. Acute myeloid leukaemia(AML) modifies the bone marrow(BM) microenvironment, impacting hematopoiesis. Here, the authors demonstrate that AML-modified BM endothelial progenitor cells(EPC) remodelling supports normal hematopoiesis after complete remission and this process is improved by the antioxidant N-acetyl-L-cysteine(NAC).