Circulating plasma cells in 10 cases of reactive plasmacytosis had a shared phenotype with early plasma cell (CD19+CD38+ CD138+ CD40+CD45+ CD11a+ CD49e−CD56−). In most cases, a minor subpopulation of CD28+ plasma cells was also detected. Reactive plasma cells were highly proliferative, suggesting the presence of circulating progenitors (plasmablasts). After CD138+ plasma cell removal, highly proliferative CD138− plasmablasts differentiated into CD138+ plasma cells within a few days. This differentiation, which was associated with increased CD38 and decreased HLA-DR expression, was further confirmed by a large increase in intracellular Ig content (associated with Ig secretion) and was concomitant with extensive secretion of interleukin-6 (IL-6). The addition of neutralizing anti–IL-6 and anti-CD126 (IL-6 receptor) monoclonal antibodies totally prevented Ig secretion and cell differentiation by inducing apoptosis of plasmablasts, which indicates that IL-6 is an essential survival factor for plasmablasts. This report provides the first characterization of normal plasmablasts and shows that their phenotype is not exactly that of multiple myeloma cells.
Recent studies have shown that two recurrent translocations, t(4;14)(p16;q32) and t(11;14)(q13;q32), define distinct entities with different prognosis in multiple myeloma (MM). We addressed the issue of whether these illegitimate IGH rearrangements could contribute to the morphological heterogeneity of the malignant plasma cells (PC). Bone marrow aspirates of 178 untreated MM cases with successful molecular cytogenetics analysis using fluorescence in situ hybridization were reviewed. PC of 25/48 (52%) patients with t(11;14) exhibited a lymphoplasmacytoid morphology. Moreover, 25/27 (93%) of the cases with this morphological profile bore the t(11;14). In addition, both cytogenetics and morphological subtypes shared higher incidence of nonsecretory MM. In contrast, 17 out of 28 cases (61%) with t(4;14) exhibited PC with diffuse chromatin pattern. Interestingly, both t(4;14) translocation and immature morphology correlated with higher incidence of high tumor mass and chromosome 13 abnormality. In conclusion, our results suggest that a particular morphology can be the signature of chromosomal abnormalities in MM.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.