Genetic abnormalities and patterns of antigenic expression in multiple myeloma.
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.
Mateo
Gema
G
Servicio de Hematología, Hospital Universitario de Salamanca, Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC, Spain.
Castellanos
Mariana
M
Rasillo
Ana
A
Gutiérrez
Norma C
NC
Montalbán
Ma Angeles
MA
Martín
Ma Luisa
ML
Hernández
Jesús Ma
JM
López-Berges
Ma Consuelo
MC
Montejano
Laura
L
Bladé
Joan
J
Mateos
Ma Victoria
MV
Sureda
Anna
A
de la Rubia
Javier
J
Díaz-Mediavilla
Joaquín
J
Pandiella
Atanasio
A
Lahuerta
Juan José
JJ
Orfao
Alberto
A
San Miguel
Jesús F
JF
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D015321:Gene Rearrangement; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology; D011003:Ploidies; D014178:Translocation, Genetic
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm