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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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Submitted October 19, 2007
Accepted March 4, 2008

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 Quijano, Antonio Lopez, Ana Rasillo, Susana Barrena, Maria Luz Sanchez, Juan Flores, Carlos Fernandez, Jose Maria Sayagues, Carlos Salvador Osuna, Nuria Fernandez, Marcos Gonzalez, Pilar Giraldo, Manuel Giralt, Maria Carmen Perez, Jose Manuel Martin-Antoran, Oliver Gutierrez, Luis Perdiguer, Joaquin Diaz Mediavilla, Manuel Gonzalez Silva, Agustin Asensio del Rio, Carlos Cervero, Jose Luis Guerra, Rosario Butron, Maria del Carmen Garcia, Julia Almeida, and Alberto Orfao*

Servicio General de Citometria, Universidad de Salamanca, Salamanca, Spain
Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain
Centro de Investigacion del Cancer (IBMCC-CSIC/USAL), Universidad de Salamanca, Salamanca, Spain
Servicio de Hematologia, Hospital Miguel Servet, Zaragoza, Spain
Servicio de Hematologia, Hospital Universitario de Salamanca, Salamanca, Spain
Servicio de Hematologia, Hospital del Rio Hortega, Valladolid, Spain
Servicio de Hematologia, Hospital de Alcaniz, Teruel, Spain
Servicio de Hematologia, Hospital Ruber Internacional, Madrid, Spain
Servicio de Hematologia, Hospital de la Linea, Cadiz, Spain
Servicio de Hematologia, Hospital San Jorge, Huesca, Spain
Servicio de Hematologia, Hospital Virgen de la Luz, Cuenca, Spain
Servicio de Hematologia, Hospital Punta de Europa, Cadiz, Spain
Servicio de Anatomia Patologica, Hospital Universitario de Salamanca, Salamanca, Spain

* Corresponding author; email: orfao{at}usal.es.

Limited knowledge exists about the impact of specific genetic abnormalities on the proliferation of neoplastic B-cells from chronic lymphoproliferative disorders (B-CLPD). 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, in comparison to 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 (DLBCL) and Burkitt lymphomas (BL). Compared to normal B-cells, neoplastic B-CLPD cells showed significantly increased S+G2/M-phase values in mantle cell lymphoma (MCL), B-chronic lymphocytic leukaemia (B-CLL), BL and some DLBCL cases. In contrast, decreased proliferation was observed in follicular lymphoma, lymphoplasmacytic lymphoma (LPL/WM) and some DLBCL patients; hairy cell leukaemia, 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, but not other cytogenetic changes, were associated with a higher percentage of S+G2/M-phase cells among LPL/WM and B-CLL cases, respectively.


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