Pathophysiology

There is intraclonal variation in the Ig gene mutation and MGUS appears to arise from a pre-germinal centre cell whose progeny pass through the germinal centre and undergo mutation. Progression to MM may be due to 268 outgrowth of a single clone. There is a continuing rate of progression to MM, WM, AL and other lymphoproliferative disorders. FISH demonstrates same MM cytogenetic abnormalities in MGUS often acquired over time. Expression microarrays show MGUS much closer to MM than to normal plasma cells. No specific trigger for progression yet identified.

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