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

Author:

Quijano Sandra123,López Antonio1,Rasillo Ana13,Barrena Susana123,Luz Sánchez Maria123,Flores Juan123,Fernández Carlos123,Sayagués José María13,Osuna Carlos Salvador4,Fernández Nuria4,González Marcos5,Giraldo Pilar4,Giralt Manuel4,Pérez Maria Carmen4,Martin-Antoran José Manuel6,Gutiérrez Oliver6,Perdiguer Luis7,Díaz Mediavilla Joaquín8,González Silva Manuel9,Asensio del Rio Agustín10,Cerveró Carlos11,Guerra José Luis11,Butrón Rosario12,del Carmen García Maria13,Almeida Julia123,Orfao Alberto123

Affiliation:

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

Abstract

Abstract 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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