What is the pathophysiology of multiple myeloma (MM)?

Updated: Sep 30, 2019
  • Author: Dhaval Shah, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

The development of MM is commonly preceded by monoclonal gammopathy of undetermined significance (MGUS), a premalignant condition that results when plasma cells undergo mutations that restore their capacity for proliferation. In MGUS, these clonal plasma cells take up less than 10% of bone marrow. The serum protein value is less than 3 g/dL and myeloma-related end-organ damage is absent. An intermediate disease stage between MGUS and MM, termed smoldering MM, is characterized by an M protein level of  3 g/dL or more and over 10% clonal plasma cells in bone marrow, but no symptoms of myeloma-related end-organ damage. [6]   .

A variety of cytogenetic abnormalities are found in MGUS and MM. Approximately half of cases are hyperdiploid, usually with extra copies of the odd-numbered chromosomes. Most of the remainder are nonhyperdiploid and are characterized by a primary translocation involving the Ig heavy-chain gene at 14q32. [6] In addition, virtually all cases involve dysregulation of the cyclin D/retinoblastoma (cyclin D/RB) pathway.  This genetic heterogeneity contributes to the rapid emergence of drug resistance in MM. [7]  

Increasing evidence suggests that the bone marrow microenvironment of tumor cells plays a pivotal role in the pathogenesis of myelomas. [8] This discovery has resulted in the expansion of treatment options.

The role of cytokines in the pathogenesis of MM is an important area of research. Interleukin (IL)-6 is also an important factor promoting the in vitro growth of myeloma cells. Other cytokines are tumor necrosis factor and IL-1b.

The pathophysiologic basis for the clinical sequelae of MM involves the skeletal, hematologic, renal, and nervous systems, as well as general processes (see below).


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