Cytogenetics and molecular studies have indicated that multiple genetic events are implicated in the pathogenesis of myeloma. In particular, IgH switch translocations are proposed to be the primary event in MGUS, with additional events contributing to transformation of the malignant clone to intramedullary myeloma. During this phase, myeloma cells produce factors that create a bone marrow microenvironment that is essential for survival, growth, and differentiation. Subsequently, secondary translocations or dys-regulation of oncogenes lead to growth independent of the bone marrow milieu and a clinical course that is aggressive with frequent extramedullary manifestation.
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