Paraproteinaemias: pathophysiology

Paraproteinaemias may be associated with benign or malignant proliferations of lymphocytes or plasma cells, including multiple myeloma, monoclonal gam mopathy of undetermined significance (MGUS) and Waldenstrom's macroglobulin aemia. Primary amyloidosis may be associated with multiple myeloma and rare ly with lymphoid malignancies, but most cases can be considered as a partic ular form of monoclonal gammopathy of undetermined significance, where the paraprotein causes damage by virtue of its amyloidogenic properties. This a rticle discusses recent advances in understanding of the biology of multipl e myeloma. Multiple myeloma is now known to arise from a post-germinal cent re B cell in the lymph node which homes to the bone marrow. Interactions wi th stromal cells in the marrow facilitate homing and growth of the myeloma cells. The stromal cells produce IL-6, which is an important growth factor for myeloma cells, while the myeloma cells produce factors such as TNF-alph a and IL-1 beta that activate osteoclasts, resulting in myeloma bone diseas e. Myeloma cells also produce vascular endothelial growth factor which resu lts in increased microvessel formation in the marrow, promoting tumour grow th. There has been interest in the possible role of the Kaposi's sarcoma as sociated herpes virus (HHV8) in multiple myeloma, following the demonstrati on of viral gene sequences in multiple myeloma marrow. However, results of further studies have been conflicting and at present there is no clear evid ence for an aetiological role of HHV8 in multiple myeloma. Cytogenetic stud ies using modern techniques have demonstrated that almost all multiple myel oma cases are cytogenetically abnormal, the predominant abnormalities being various translocations involving chromosome 14q and deletions of chromosom e 13. 14q translocations are equally common in monoclonal gammopathy of und etermined significance, but deletions of chromosome 13 seem to be associate d with progression to multiple myeloma, and also have powerful prognostic s ignificance for survival in multiple myeloma patients.