Multiple myeloma pathogenesis: Blame it on the microenvironment

摘要

Multiple myeloma (MM) is a postgerminal center B-cell neoplasm, characterized by the accumulation of clonal plasma cells in bone marrow and extramedullary sites along with a monoclonal protein in serum and/or urine. All cases of MM evolve from a premalignant condition - monoclonal gammopathy of undetermined significance (MGUS). MGUS progresses to smouldering MM (SMM) and finally to symptomatic MM requiring therapy at the rate of 1% per year. Given that not all patients with MGUS evolve to MM, it becomes relevant to identify patients who are at a risk of progression to MM. Studies examining neoplastic plasma cells from MM and MGUS, have not found significant differences in genetic abnormalities, suggesting that these genetic changes are early events in MM. In some of the MGUS patients, the neoplastic cells re-program the microenvironment (bone marrow stromal cells, osteoclasts, osteoblasts, adhesion molecules, cytokines, growth factors, and extracellular matrix) to promote tumor progression and development of myeloma.