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Pathobiology of multiple myeloma

S Vincent Rajkumar, MD
Section Editor
Robert A Kyle, MD
Deputy Editor
Rebecca F Connor, MD


Multiple myeloma (MM) is a malignant plasma cell disorder that accounts for approximately 10 percent of all hematologic malignancies. It is an incurable disease and the cause of about 20 percent of deaths from hematologic malignancy and 2 percent of deaths from all cancers. (See "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma", section on 'Epidemiology'.)

MM is thought to evolve from an asymptomatic pre-malignant stage of clonal plasma cell proliferation termed monoclonal gammopathy of undetermined significance (MGUS). MGUS is present in over 3 percent of the population above the age of 50, and progresses to myeloma or a related malignancy at a rate of 1 percent per year. (See "Diagnosis of monoclonal gammopathy of undetermined significance" and "Laboratory methods for analyzing monoclonal proteins".)

While MGUS is asymptomatic, MM is characterized by end organ damage, which includes hypercalcemia, renal dysfunction, anemia, or lytic bone lesions. In some patients, an intermediate asymptomatic but more advanced pre-malignant stage referred to as smoldering multiple myeloma (SMM) can be recognized clinically. (See "Overview of the management of multiple myeloma".)

The pathobiology of MM will be reviewed here. The clinical and laboratory manifestations, diagnosis, and treatment of MM are discussed separately. (See "Overview of the management of multiple myeloma".)


Multiple myeloma (MM) appears to arise from the malignant transformation of post-germinal center plasma cells [1,2]. The post-germinal ancestry of these cells is principally supported by the identification of somatic mutations in the variable region of the immunoglobulin genes, which serve as a marker of germinal center transit. These cells also display ongoing somatic mutations, which reflect the pressure of antigen selection encountered by post-germinal center lymphocytes. By definition, class switching is demonstrated in IgG and IgA MM, but not in IgM MM. (See "Immunoglobulin genetics", section on 'Immunoglobulin class-switching'.)

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Literature review current through: Nov 2017. | This topic last updated: Nov 23, 2017.
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