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Genetic Abnormalities and Patterns of Antigenic Expression in Multiple Myeloma

Authors' Affiliations: ¹ Servicio de Hematología, Hospital Universitario de Salamanca, ² Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC; ³ Servicio General de Citometría, Universidad de Salamanca; ⁴ Hospital 12 de Octubre; ⁵ Hospital Clínico Universitario, Madrid, Spain; ⁶ Hospital Clínic; ⁷ Hospital Sant Pau i Santa Creu, Barcelona, Spain; and ⁸ Hospital La Fe, Valencia, Spain

Requests for reprints: Jesús San Miguel Izquierdo, Servicio de Hematolog ía, Hospital Universitario de Salamanca, Paseo San Vicente 58-182, 37007 Salamanca, Spain. Phone: 34-923-291384; Fax: 34-923-294624; E-mail: sanmigiz{at}usal.es.

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^– and CD117^– 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^– cases. IGH translocation to 11q13 was associated with reactivity for CD20 (P < 0.001), down-regulation 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^– and CD117^– 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.

Key Words: myeloma • immunophenotype • DNA ploidy • chromosomal abnormalities • FISH

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