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 Blood, 15 May 2008, Vol. 111, No. 10, pp. 5130-5141.
Prepublished online as a Blood First Edition Paper on March 12, 2008; DOI 10.1182/blood-2007-10-119289.

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NEOPLASIA

Association between the proliferative rate of neoplastic B cells, their maturation stage, and underlying cytogenetic abnormalities in B-cell chronic lymphoproliferative disorders: analysis of a series of 432 patients

Sandra Quijano13, Antonio López1, Ana Rasillo1,3, Susana Barrena13, Maria Luz Sánchez13, Juan Flores13, Carlos Fernández13, José María Sayagués1,3, Carlos Salvador Osuna4, Nuria Fernández4, Marcos González5, Pilar Giraldo4, Manuel Giralt4, Maria Carmen Pérez4, José Manuel Martin-Antoran6, Oliver Gutiérrez6, Luis Perdiguer7, Joaquín Díaz Mediavilla8, Manuel González Silva9, Agustín Asensio del Rio10, Carlos Cerveró11, José Luis Guerra11, Rosario Butrón12, Maria del Carmen García13, Julia Almeida13, and Alberto Orfao13

1 Servicio General de Citometría, 2 Departamento de Medicina, and 3 Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigacion del Cáncer–Consejo Superior de Investigaciones Cientificas (IBMCC-CSIC), Universidad de Salamanca (USAL), Salamanca; 4 Servicio de Hematología, Hospital Miguel Servet, Zaragoza; 5 Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca; 6 Servicio de Hematología, Hospital del Río Hortega, Valladolid; 7 Servicio de Hematología, Hospital de Alcañiz, Teruel; 8 Servicio de Hematología, Hospital Ruber Internacional Madrid, Madrid; 9 Servicio de Hematología, Hospital de la Línea, Cádiz; 10 Servicio de Hematología, Hospital San Jorge, Huesca; 11 Servicio de Hematología, Hospital Virgen de la Luz, Cuenca; 12 Servicio de Hematología, Hospital Punta de Europa, Cádiz; and 13 Servicio de Anatomía Patológica, Hospital Universitario de Salamanca, Salamanca, Spain

Limited knowledge exists about the impact of specific genetic abnormalities on the proliferation of neoplastic B cells from chronic lymphoproliferative disorders (B-CLPDs). Here we analyze the impact of cytogenetic abnormalities on the proliferation of neoplastic B cells in 432 B-CLPD patients, grouped according to diagnosis and site of sampling, versus their normal counterparts. Overall, proliferation of neoplastic B cells highly varied among the different B-CLPD subtypes, the greatest numbers of proliferating cells being identified in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Compared with normal B cells, neoplastic B-CLPD cells showed significantly increased S + G2/M-phase values in mantle cell lymphoma (MCL), B-chronic lymphocytic leukemia (B-CLL), BL, and some DLBCL cases. Conversely, decreased proliferation was observed in follicular lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), and some DLBCL patients; hairy cell leukemia, splenic marginal zone, and MALT-lymphoma patients showed S + G2/M phase values similar to normal mature B lymphocytes from LN. Interestingly, in B-CLL and MCL significantly higher percentages of S + G2/M cells were detected in BM versus PB and in LN versus BM and PB samples, respectively. In turn, presence of 14q32.3 gene rearrangements and DNA aneuploidy, was associated with a higher percentage of S + G2/M-phase cells among LPL/WM and B-CLL cases, respectively.


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