Modifications of the mouse bone marrow microenvironment favor angiogenesis and correlate with disease progression from asymptomatic to symptomatic multiple myeloma

摘要: While multiple myeloma (MM) is almost invariably preceded by asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering MM (SMM), the alterations bone marrow (BM) microenvironment that establish progression to symptomatic disease are circumstantial. Here we show in Vk*MYC mice harboring oncogene-driven plasma cell proliferative disorder, appearance associated with substantial modifications BM microenvironment, including a progressive accumulation both CD8+ and CD4+ T cells dominant helper type 1 (Th1) response. Progression from was characterized further accrual reduced Th1 persistently increased Th2 cytokine production, which CD206+Tie2+ macrophages, pro-angiogenic cytokines microvessel density (MVD). Notably, MVD also at diagnosis MGUS SMM patients subsequently progressed when compared remained quiescent. These findings suggest multistep pathogenic process MM, immune system may contribute angiogenesis progression. They initiating large multicenter study investigate as prognostic factor for outcome this disease.