Multiple myeloma in the marrow: pathogenesis and treatments.

Document Type


Publication Date



Maine Medical Center Research Institute, Surgery

Journal Title

Annals of the New York Academy of Sciences

MeSH Headings

Animals, Antineoplastic Agents, Bone Marrow, Bone Marrow Cells, Bone Remodeling, Humans, Models, Biological, Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Mutation, Neoplasm Proteins, Precision Medicine, Stem Cell Niche, Stem Cell Transplantation, Transplantation, Autologous, Tumor Burden, Tumor Microenvironment


Multiple myeloma (MM) is a B cell malignancy resulting in osteolytic lesions and fractures. In the disease state, bone healing is limited owing to increased osteoclastic and decreased osteoblastic activity, as well as an MM-induced forward-feedback cycle where bone-embedded growth factors further enhance tumor progression as bone is resorbed. Recent work on somatic mutation in MM tumors has provided insight into cytogenetic changes associated with this disease; the initiating driver mutations causing MM are diverse because of the complexity and multitude of mutations inherent in MM tumor cells. This manuscript provides an overview of MM pathogenesis by summarizing cytogenic changes related to oncogenes and tumor suppressors associated with MM, reviewing risk factors, and describing the disease progression from monoclonal gammopathy of undetermined significance to overt MM. It also highlights the importance of the bone marrow microenvironment (BMM) in the establishment and progression of MM, as well as associated MM-induced bone disease, and the relationship of the bone marrow to current and future therapeutics. This review highlights why understanding the basic biology of the healthy and diseased BMM is crucial in the quest for better treatments and work toward a cure for genetically diverse diseases such as MM.



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