Genetic Abnormalities and Patterns of Antigenic Expression in Multiple Myeloma

Abstract

Myelomatous plasma cells show a high heterogeneity both in their immunophenotypic characteristics as well as in their cytogenetic features. Thus far, no extensive studies have been carried out to explore whether such antigenic diversity is associated with specific genetic characteristics.We have investigated the relationship between the immunophenotypic profile at plasma cell and both their DNA ploidy status (evaluated by flow cytometry) and specific genetic features (ascertained by fluorescence in situ hybridization) in a large series of 915 patients with newly diagnosed multiple myeloma. The non-hyperdiploid multiple myeloma group (n = 454, 52%) was associated with a significantly higher frequency of positivity for CD28 and CD20 as well as a higher incidence of CD56 À and CD117À cases (P < 0.001). Remarkably, 13q deletion and immunoglobulin heavy chain (IGH) gene rearrangements, which were significantly more common in non-hyperdiploid multiple myeloma, showed a strong association with CD117 À cases. IGH translocation to 11q13 was associated with reactivity for CD20 (P < 0.001), downregulation of CD56 (P < 0.001), and lack of expression of CD117 (P = 0.001). By contrast, IGH translocations to other chromosome partners were almost exclusively found among CD20 À and CD117 À cases (P < 0.001). These results suggest that genetic categories in multiple myeloma exhibit particular immunophenotypic profiles which in turn are strongly associated with the DNA ploidy status.

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

“…1,4,25,26,29 It has also been described that some of these features are associated with specific phenotypic profiles, 7,30 but in contrast to other hematological malignancies, 31,32 in MM the antigenic profile of malignant cells is not usually taken into account for patient risk stratification. 33 We have recently reported that CD19 expression in MM-PCs is an adverse prognostic marker.…”

Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell‐related disorders

“…In turn, absence of CD117 expression is associated with a higher frequency of non-hyperdiploid MM, t(4;14) and del (13q) (17,36,38). Additional phenotypic-genotypic associations have been also reported, such as those found between t(11;14) and both a CD20 þ and CD56 À immunophenotype (38). However, it should be noted that these associations are not strong enough to consider immunophenotyping as a valuable tool for the rapid diagnostic screening of genetic abnormalities in patients with myeloma (10).…”

“…Phenotypically aberrant PC typically show: (i) underexpression of CD19, CD27, CD38, and CD45; (ii) overexpression of CD28, CD33, and CD56; and (iii) asynchronous expression of CD20, CD117, and surface immunoglobulins (sIg) ( Table 2) (13,14,(18)(19)(20)(21)23,35,(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49). Immunophenotypic panels containing simultaneous stainings for at least four markers in multicolor combinations are typically required for the identification and characterization of PC (50).…”

“…As described for other hematological malignancies, the prognostic impact of these phenotypic markers could be related to the underlying cytogenetic abnormalities. In fact, it has been shown that CD28 expression on clonal PC is associated with non-hyperdiploid MM (17,38), t(4;14) and del(17p) (17). In turn, absence of CD117 expression is associated with a higher frequency of non-hyperdiploid MM, t(4;14) and del (13q) (17,36,38).…”

“…In fact, it has been shown that CD28 expression on clonal PC is associated with non-hyperdiploid MM (17,38), t(4;14) and del(17p) (17). In turn, absence of CD117 expression is associated with a higher frequency of non-hyperdiploid MM, t(4;14) and del (13q) (17,36,38). Additional phenotypic-genotypic associations have been also reported, such as those found between t(11;14) and both a CD20 þ and CD56 À immunophenotype (38).…”