Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission
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 m...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55051-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841559303716077568 |
|---|---|
| author | 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 Xiao-Jun Huang |
| author_facet | 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 Xiao-Jun Huang |
| author_sort | Tong Xing |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9c2e656df9c84a86b27b3d6f2ea49cbf |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9c2e656df9c84a86b27b3d6f2ea49cbf2025-01-05T12:36:07ZengNature PortfolioNature Communications2041-17232024-12-0115111310.1038/s41467-024-55051-xBone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete RemissionTong Xing0Li-Juan Hu1Hong-Yan Zhao2Chen-Yuan Li3Zhen-Kun Wang4Meng-Zhu Shen5Zhong-Shi Lyu6Jing Wang7Yu Wang8Hao Jiang9Qian Jiang10Ying-Jun Chang11Xiao-Hui Zhang12Yuan Kong13Xiao-Jun Huang14Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityAbstract 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.https://doi.org/10.1038/s41467-024-55051-x |
| spellingShingle | 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 Xiao-Jun Huang Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission Nature Communications |
| title | Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission |
| title_full | Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission |
| title_fullStr | Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission |
| title_full_unstemmed | Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission |
| title_short | Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission |
| title_sort | bone marrow endothelial progenitor cells remodelling facilitates normal hematopoiesis during acute myeloid leukemia complete remission |
| url | https://doi.org/10.1038/s41467-024-55051-x |
| work_keys_str_mv | AT tongxing bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT lijuanhu bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT hongyanzhao bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT chenyuanli bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT zhenkunwang bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT mengzhushen bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT zhongshilyu bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT jingwang bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT yuwang bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT haojiang bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT qianjiang bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT yingjunchang bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT xiaohuizhang bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT yuankong bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission AT xiaojunhuang bonemarrowendothelialprogenitorcellsremodellingfacilitatesnormalhematopoiesisduringacutemyeloidleukemiacompleteremission |