MM arises from a post germinal centre B cell (probably in LN or spleen) 272 that has undergone antigen selection, VDJ recombination, somatic hypermutation of V regions and switch-recombination of IgH genes. Aberrant class-switch recombination may contribute to neoplastic transformation (IgH translocations common in MM). BM microenvironment critical to clonal expansion. Secretion of IL-6, IL-1, TNF-a and RANK-ligand stimulate MM proliferation and osteoclast proliferation and activation (causes bone destruction plus hypercalcaemia). BM infiltration causes anaemia. Immuneparesis of normal Ig production predisposes to infection. Physico-chemical properties of paraprotein determine amyloid deposition, renal damage and hyperviscosity (IgA and IgG4).

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