2. Academic Validation
  3. Leukemia-expanded splenic CD81+ erythroblasts potentiate disease progression in mice by reshaping leukemic cell metabolism

Leukemia-expanded splenic CD81+ erythroblasts potentiate disease progression in mice by reshaping leukemic cell metabolism

  • J Clin Invest. 2025 Dec 15;135(24):e193082. doi: 10.1172/JCI193082.
Yue Li 1 2,  Jiaxuan Cao 1 3,  Jingyuan Tong 1,  Peixia Tang 1,  Haoran Chen 4,  Guohuan Sun 1,  Zining Yang 1,  Xiaoru Zhang 1,  Fang Dong 1,  Shangda Yang 1,  Jie Gao 1,  Xiangnan Zhao 1,  Jinfa Ma 1,  Di Wang 1,  Lei Zhang 1,  Lin Wang 4,  Tao Cheng 1,  Hui Cheng 1,  Lihong Shi 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Institutes of Health Science, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
  • 2 Department of Hematology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
  • 3 Department of Oncology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, China.
  • 4 State Key Laboratory of Common Mechanism Research for Major Disease, Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
PMID: 41392984 DOI: 10.1172/JCI193082
Abstract

During the progression of acute myeloid leukemia (AML), extramedullary hematopoiesis (EMH) compensates for impaired bone marrow hematopoiesis. However, the specific cellular dynamics of EMH and its influence on AML progression remain poorly understood. In this study, we identified a substantial expansion of the CD81+ erythroblast subpopulation (CD81+ Erys) in the spleens of AML mice, which promoted AML cell proliferation and reduced survival. Mechanistically, CD81+ Erys secrete elevated levels of macrophage migration-inhibitory factor (MIF), which interacted with the CD74 receptor on AML cells, activating the mTORC1 signaling pathway and upregulating Egln3. Consequently, AML cells cocultured with CD81+ Erys exhibited reprogrammed phospholipid metabolism, characterized by an increased phospholipid-to-lysophospholipid ratio. Modulating this metabolic shift, either by supplementing exogenous lysophospholipids or depleting Egln3 in AML cells, restored the phospholipid balance and mitigated the protumorigenic effects induced by CD81+ Erys. Overall, our findings elucidate the molecular crosstalk between erythroblasts and AML cells, extend our insights into the mechanisms driving AML progression, and suggest potential therapeutic strategies.

Keywords

Cell biology; Hematology; Leukemias; Metabolism.

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