Interventional Techniques for the Ablation and Augmentation of Extraspinal Lytic Bone Metastases.

Journal and index pages often block iframe embedding. This reader keeps the evidence details in Orthonotes and leaves the source page one click away.

Abstract

Conflict of interest statement: Conflict of Interest None. 18. Nat Commun. 2025 Jan 31;16(1):1206. doi: 10.1038/s41467-025-56506-5. EZH2 serves as a viable therapeutic target for myeloma-induced osteolytic bone destruction. Liu R(#)(1), Li Z(#)(2), Chen R(1), Fang Z(3)(4), Liu Z(5), Liu H(6)(7)(8)(9). Author information: (1)Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China. (2)School of Life Sciences, Anhui Medical University, Hefei, Anhui, China. (3)Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, China. (4)Department of Hematology, Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, China. (5)Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. zqliu@sdfmu.edu.cn. (6)Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China. huanliu@xmu.edu.cn. (7)Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, China. huanliu@xmu.edu.cn. (8)Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, China. huanliu@xmu.edu.cn. (9)Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong, China. huanliu@xmu.edu.cn. (#)Contributed equally Myelomatous bone disease is a complication characterized by lytic bone lesions, reduced bone formation, bone pain, and increased fracture risk. Understanding these underlying mechanisms is crucial for developing effective therapeutic approaches. Here we show the role of enhancer of zeste homolog 2 (EZH2) in bone lesions induced by myeloma cells. Our research reveals that cytokines produced by myeloma-associated adipocytes activate the expression of EZH2 in myeloma cells. Furthermore, we find that EZH2 forms a transcriptional repression complex with transcription factor AP2α. This complex promotes trimethylation at lysine 27 of histone H3 (H3K27me3) in the promoter region of the tumor suppressor gene EMP1, resulting in transcriptional silencing. EMP1 silencing leads to increased myeloma cell proliferation and the concomitant secretion of osteolytic cytokines that contribute to bone destruction. Importantly, EZH2 inhibitors effectively treat myeloma-induced osteolytic lesions. Thus, targeting EZH2 represents a potential therapeutic strategy for preventing and managing myeloma bone disease. © 2025. The Author(s). DOI: 10.1038/s41467-025-56506-5 PMCID: PMC11782520