Regulatory Effect and Mechanism of Erythroblastic Island Macrophages on Anemia in Patients with Newly Diagnosed Multiple Myeloma

Abstract

Hao Huang,1,* Peng-Yang Yu,1,* Chen Wei,2 Yang-Wei Li,3 Li-Jie Liang,1 Yu-Zhang Liu,1 Li-Na Liu,1 Bai-Jun Fang,1 Yao-Mei Wang1 1Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 2Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 3Central Laboratory, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yao-Mei Wang; Bai-Jun Fang, Email [email protected]; [email protected]: To examine the clinical characteristics and anemia-related factors in patients with newly diagnosed multiple myeloma (NDMM), as well as the effect and mechanism of erythroblastic islands (EBIs) and EBI macrophages in NDMM patients with anemia.Methods: We collected and analyzed clinical data to find anemia-related factors. Using flow cytometry, the numbers and ratios of erythroblasts and EBI macrophages were determined. RNA sequencing (RNA-seq) was used to determine the differences of EBI macrophages in NDMM patients with or without anemia.Results: Based on the clinical characteristics of NDMM patients with anemia, MCV, abnormal levels of albumin, osteolytic lesions, and Durie-Salmon (DS) stage are risk factors for anemia. Patients with anemia have fewer erythroblasts, erythroblastic islands (EBIs), and EBI macrophages in their bone marrow than patients without anemia. RNA-seq analysis of EBI macrophages from the bone marrow of patients with and without anemia revealed that macrophages from patients with anemia are impaired and tend to promote the production of interleukin-6, which has been demonstrated to be an essential survival factor of myeloma cells and protects them from apoptosis.Conclusion: In NDMM patients with anemia, EBI macrophages are impaired, which causes anemia in those patients. Our finding highlights the significance of EBI macrophages in anemia in NDMM patients and provides a new strategy for recovery from anemia in these patients.Keywords: anemia, central macrophages, erythroblastic islands, erythropoiesis, multiple myeloma

Keywords

• anemia
• central macrophages
• erythroblastic islands
• erythropoiesis
• multiple myeloma.