Molecular Pathogenesis of Multiple Myeloma: Clinical Implications

Francesco Maura; Peter Leif Bergsagel

doi:10.1016/j.hoc.2023.12.010

Molecular Pathogenesis of Multiple Myeloma: Clinical Implications

Hematol Oncol Clin North Am. 2024 Apr;38(2):267-279. doi: 10.1016/j.hoc.2023.12.010. Epub 2024 Jan 9.

Authors

Francesco Maura¹, Peter Leif Bergsagel²

Affiliations

¹ University of Miami, 1120 Northwest 14th Street, Miami, FL 33136, USA. Electronic address: fxm557@med.miami.edu.
² Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA. Electronic address: Bergsagel.leif@mayo.edu.

PMID: 38199896
DOI: 10.1016/j.hoc.2023.12.010

Abstract

Multiple myeloma is a malignancy of bone-marrow-localized, isotype-switched plasma cells that secrete a monoclonal immunoglobulin and cause hyperCalcemia, Anemia, Renal failure, and lytic Bone disease. It is preceded, often for decades, by a relatively stable monoclonal gammopathy lacking these clinical and malignant features. Both conditions are characterized by the presence of types of immunoglobulin heavy gene translocations that dysregulate a cyclin D family gene on 11q13 (CCND1), 6p21 (CCND3), or 12q11 (CCND2), a maf family gene on 16q23 (MAF), 20q11 (MAFB), or 8q24 (MAFA), or NSD2/FGFR3 on 4p16, or the presence of hyperdiploidy. Subsequent loss of function of tumor suppressor genes and mutations activating MYC, RAS, NFkB, and cell cycle pathways are associated with the progression to malignant disease.

Keywords: Hyperdiploidy; MYC; Monoclonal gammopathy of undetermined significance (MGUS); Multiple myeloma (MM); NFkB; Plasma cell (PC); RAS; Smoldering multiple myeloma (SMM).

Publication types

Review

MeSH terms

Gene Rearrangement
Humans
Immunoglobulins / genetics
Monoclonal Gammopathy of Undetermined Significance* / genetics
Multiple Myeloma* / genetics
Multiple Myeloma* / pathology
Multiple Myeloma* / therapy
Mutation
Translocation, Genetic

Substances

Immunoglobulins