Angiogenesis in B cell lymphoproliferative diseases. Biological and clinical studies.

Abstract

Angiogenesis is a necessary step in solid tumor progression (growth, invasion and metastasis) with which it correlates and is indicative of an unfavourable prognosis. We observed bone marrow angiogenesis in patients with active multiple myeloma (MM), though not in patients with non-active MM nor with monoclonal gammopathies of undetermined significance (MGUS). Microvessel density increased in parallel with the labeling index (LI%)--an indicator of plasma cell proliferating activity that correlates with prognosis--and defined a risk of MM progression in much the same way as LI% itself. Consequently, bone marrow angiogenesis could be an indication for unfavourable prognosis in MGUS and MM. Angiogenesis has also been demonstrated in lymph nodes involved by B cell non Hodgkin's lymphoma (B-NHL) belonging to the Working Formulation intermediate-grade (diffuse subtypes), and high-grade categories, but not in the low-grade and intermediate-grade (follicular subtype) categories. It correlated with the B-NHL cell proliferating activity, since large increments in this activity have already been demonstrated in intermediate- and high-grade vs low-grade tumors. Active MM, intermediate-grade, diffuse subtypes, and high-grade B-NHLs correspond to the vascular phases of B cell lymphoproliferative diseases, and could thus be assimilated to locally invasive and metastatic solid tumors. Similarly to solid tumors during these stages of progression, tumor B cells are also capable of inducing angiogenesis, both directly and indirectly by activating the inflammation infiltrate--a possibility that was first demonstrated by means of B-NHL implants onto the chick embryo chorioallantoic membrane. Anti-angiogenic therapy can be envisaged as a possible future development.