ENAapplication/xmlftp.sra.ebi.ac.uk/vol1/fastq/SRR706/002/SRR7062902/SRR7062902.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR706/004/SRR7062904/SRR7062904.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR706/000/SRR7062900/SRR7062900.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR706/001/SRR7062901/SRR7062901.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR706/005/SRR7062905/SRR7062905.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR706/003/SRR7062903/SRR7062903.fastq.gzprimaryOK2000000GenomicsMD Anderson Cancer Centerhttps://www.ebi.ac.uk/ena/browser/view/PRJNA453494Homo sapiensMultiple myeloma is characterized by osteolytic lesions caused by osteoclast-mediated bone resorption and reduced bone formation. A unique feature of myeloma is a failure of bone healing following successful treatment. Identification of increased adipocyte numbers in marrow of successfully treated patients led us to demonstrate that normal marrow adipocytes, when co-cultured with myeloma cells, are reprogrammed and produce adipokines that activate osteoclastogenesis and suppress osteoblastogenesis. These adipocytes have reduced expression of peroxisome proliferator-activated receptor (PPAR) mediated by recruitment of polycomb-repressive complex 2 (PRC2) via specificity protein 1, which modifies PPAR promoter methylation at trimethyl lysine-27 histone H3. We confirmed the importance of PPAR methylation by demonstrating that adipocyte-specific knockout of EZH2, a member of the PRC2, prevents adipocyte reprogramming and reverses bone changes in vivo. These results define a heretofore unrecognized role for adipocytes in genesis of myeloma-associated bone disease and that reversal of adipocyte reprogramming has therapeutic implications. Overall design: Define a heretofore unrecognized role for adipocytes in genesis of myeloma-associated bone diseaseENArare bone disease related to a common gene or pathway defect., Disease, bone element disease or disorder, VAMAS2, Myeloma, Multiple myeloma (disorder), malignant, Kahler's disease, "skeletal disease" RELATED [], Cell, plasma cell, Fat Cells, Concept, Al amyloidosis, multiple myeloma, Bone Disease, disorder of bone element, Role Concept, myelomatosis, Roles, myeloid neoplasm of plasma cell, [M]Plasma cell myeloma, Diseases, Role, disease or disorder of bone element, Concepts, bone disorder, NOS, Myelomatosis, multiple myeloma/plasma cell myeloma, bone element disease, MULT MYELM W/O REMISSION, morphology (morphologic abnormality), CWH3, Plasmacytic myeloma, Adipocyte, systemic, amyloidosis, Multiple myeloma, skeletal disease, HFH2, Hfh2, susceptibility to, Somatic mutation, myeloma, medullary plasmacytoma, Multiple myeloma without mention of remission, disease of bone element, resistance to, no ICD-O subtype, multiple, Plasma Cell Myeloma, Fat Cell, no ICD-O subtype (morphologic abnormality), Lipocytes, Cells, Role Concepts, plasma cell myeloma, Lipocyte, Multiple myeloma (clinical), Fat, AIS1, Genesis, Bone, myeloma - multiple, Kahler disease, plasma cell myeloid neoplasmrare bone disease related to a common gene or pathway defect., Disease, bone element disease or disorder, VAMAS2, Myeloma, Multiple myeloma (disorder), malignant, Kahler's disease, "skeletal disease" RELATED [], Cell, plasma cell, Fat Cells, Concept, Al amyloidosis, multiple myeloma, Bone Disease, disorder of bone element, Role Concept, myelomatosis, Roles, myeloid neoplasm of plasma cell, [M]Plasma cell myeloma, Diseases, Role, disease or disorder of bone element, Concepts, bone disorder, NOS, Myelomatosis, multiple myeloma/plasma cell myeloma, bone element disease, MULT MYELM W/O REMISSION, morphology (morphologic abnormality), CWH3, Plasmacytic myeloma, Adipocyte, systemic, amyloidosis, Multiple myeloma, skeletal disease, HFH2, Hfh2, susceptibility to, Somatic mutation, myeloma, medullary plasmacytoma, Multiple myeloma without mention of remission, disease of bone element, resistance to, no ICD-O subtype, multiple, Plasma Cell Myeloma, Fat Cell, no ICD-O subtype (morphologic abnormality), Lipocytes, Cells, Role Concepts, plasma cell myeloma, Lipocyte, Multiple myeloma (clinical), Fat, AIS1, Genesis, Bone, myeloma - multiple, Kahler disease, plasma cell myeloid neoplasm0.00.00.00.00.00falseReprogrammed marrow adipocytes: an unexpected role in the genesis of myeloma-induced bone disease (ChIP-Seq)Reprogrammed marrow adipocytes: an unexpected role in the genesis of myeloma-induced bone disease (ChIP-Seq)2022-05-122018-04-27PRJNA453494GSE113642311426799606