title: Multiple myeloma in the marrow: pathogenesis and treatments.
abstract: 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.
authors.affiliation: Maine Medical Center Research Institute, Scarborough, Maine.
authors.forename: Heather
authors.initials: H
authors.lastname: Fairfield
authors.affiliation: Maine Medical Center Research Institute, Scarborough, Maine.
authors.forename: Carolyne
authors.initials: C
authors.lastname: Falank
authors.affiliation: University of Maine, Orono, Maine.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Avery
authors.affiliation: Maine Medical Center Research Institute, Scarborough, Maine.|University of Maine, Orono, Maine.
authors.forename: Michaela R
authors.initials: MR
authors.lastname: Reagan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016723:Bone Remodeling / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D057285:Precision Medicine / Q000639:trends; D055153:Stem Cell Niche; D033581:Stem Cell Transplantation / Q000639:trends; D014182:Transplantation, Autologous / Q000639:trends; D047368:Tumor Burden / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins
keywords: Fairfield, H., C. Falank, L. Avery & M. R. Reagan. 2016. Multiple myeloma in the marrow: pathogenesis and treatments. In “MARROW,” ed. by M. Zaidi. Ann. N.Y. Acad. Sci. 1364: 32-51.; bone marrow; bone marrow niche; multiple myeloma; treatments