Multiple myeloma in the marrow: pathogenesis and treatments

Ann N Y Acad Sci. 2016 Jan;1364(1):32-51. doi: 10.1111/nyas.13038.


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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism
  • Bone Marrow / pathology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Bone Remodeling / drug effects
  • Humans
  • Models, Biological*
  • Monoclonal Gammopathy of Undetermined Significance / drug therapy
  • Monoclonal Gammopathy of Undetermined Significance / genetics
  • Monoclonal Gammopathy of Undetermined Significance / metabolism
  • Monoclonal Gammopathy of Undetermined Significance / pathology
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Multiple Myeloma / therapy
  • Mutation
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Precision Medicine / trends
  • Stem Cell Niche
  • Stem Cell Transplantation / trends
  • Transplantation, Autologous / trends
  • Tumor Burden / drug effects
  • Tumor Microenvironment* / drug effects


  • Antineoplastic Agents
  • Neoplasm Proteins