Clinical significance of CD81 expression by clonal plasma cells in high-risk smoldering and symptomatic multiple myeloma patients

Abstract

on behalf of the GEM (Grupo Españ ol de Mieloma)/PETHEMA (Programa para el Estudio de la Terapé utica en Hemopatías Malignas) cooperative study groupsThe presence of CD19 in myelomatous plasma cells (MM-PCs) correlates with adverse prognosis in multiple myeloma (MM). Although CD19 expression is upregulated by CD81, this marker has been poorly investigated and its prognostic value in MM remains unknown. We have analyzed CD81 expression by multiparameter flow cytometry in MM-PCs from 230 MM patients at diagnosis included in the Grupo Españ ol de Mieloma (GEM)05465years trial as well as 56 high-risk smoldering MM (SMM). CD81 expression was detected in 45% (103/230) MM patients, and the detection of CD81 þ MM-PC was an independent prognostic factor for progression-free (hazard ratio ¼ 1.9; P ¼ 0.003) and overall survival (hazard ratio ¼ 2.0; P ¼ 0.02); this adverse impact was validated in an additional series of 325 transplant-candidate MM patients included in the GEM05 o65 years trial. Moreover, CD81þ SMM (n ¼ 34/56, 57%) patients had a shorter time to progression to MM (P ¼ 0.02). Overall, our results show that CD81 may have a relevant role in MM pathogenesis and represent a novel adverse prognostic marker in myeloma.

Multiparameter flow cytometry for staging of solitary bone plasmacytoma: new criteria for risk of progression to myeloma

“…Overall, these results suggest similar phenotypic profiles of BM clonal PCs from SP patients vs monoclonal gammopathy of undetermined significance or MM. 10,11 However, (in contrast to MM) both clonal and normal PCs coexist within the BMPC compartment. In fact, although in SBP patients median percentage of clonal PCs exceeds that of normal PCs (66% vs 34%), the opposite pattern was found among EMP cases (74% median normal PCs).…”

“…Data acquisition was performed in a 2-step procedure, as previously described. 10,11 Patients were defined as flow-positive when $20 PCs were detectable by MFC, at a sensitivity level of 10 24 .…”

“…10,11 Briefly, a backbone antigen combination including CD19, CD38, CD45, and CD56 was systematically evaluated, allowing for identification of the BMPC compartment on the basis of strong CD38 expression and intermediate side-scatter signal, and detection of clonal PCs by the recognition of aberrant phenotypic expression profiles (supplemental Table 1, see supplemental Data available at the Blood Web site). Data acquisition was performed in a 2-step procedure, as previously described.…”

Circulating clonotypic B cells in multiple myeloma and monoclonal gammopathy of undetermined significance

“…Multiparameter flow cytometry immunophenotypic studies were performed as recently described [28][29][30][31] (and detailed in the Online Supplementary Methods) in both bone marrow and peripheral blood samples. Fluorescence-activated cell sorting (FACS) was used to purify bone marrow M-PC as well as peripheral blood B-cell subsets and normal PC (N-PC); whenever present, circulating M-PC were also purified.…”

Utility of Flow Cytometry to Classify Abnormal Plasma Cell Populations in Marrow Samples Collected from Patients with Putative Plasma Cell Neoplasms

“…Conversely, only very few cases of MGUS express CD28 [4], while this marker is expressed brightly in MM. Similarly, CD81 is brightly expressed by myeloma cells in a subset of patients, where it may be associated with CD19 co-expression, and poor clinical outcome [9]. CD229 surface expression is found on myeloma cells and B cells, in a regenerating and transplant marrow; however, the intensity of CD229 staining is brighter in myeloma cells than non-neoplastic B cells, regardless of disease stage or current treatment [10].…”