Open Access Review

Intrinsic and extrinsic factors influencing the clinical course of B-cell chronic lymphocytic leukemia: prognostic markers with pathogenetic relevance

Michele Dal-Bo1, Francesco Bertoni2, Francesco Forconi3, Antonella Zucchetto1, Riccardo Bomben1, Roberto Marasca4, Silvia Deaglio5, Luca Laurenti6, Dimitar G Efremov7, Gianluca Gaidano8, Giovanni Del Poeta9 and Valter Gattei1*

Author Affiliations

1 Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy

2 Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

3 Division of Hematology and Transplant, Department of Clinical Medicine and Immunological Sciences, University of Siena, Siena, Italy

4 Division of Hematology – Department of Oncology and Hematology-University of Modena and Reggio Emilia, Modena, Italy

5 Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry and CeRMS, University of Turin, Turin, Italy

6 Hematology Institute, Catholic University "Sacro Cuore", Rome, Italy

7 Molecular Hematology, ICGEB Outstation-Monterotondo, Rome, Italy

8 Division of Hematology – Department of Clinical and Experimental Medicine & BRMA – Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

9 Chair of Hematology, S.Eugenio Hospital and University of Tor Vergata, Rome, Italy

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Journal of Translational Medicine 2009, 7:76  doi:10.1186/1479-5876-7-76

Published: 28 August 2009

Abstract

B-cell chronic lymphocytic leukemia (CLL), the most frequent leukemia in the Western world, is characterized by extremely variable clinical courses with survivals ranging from 1 to more than 15 years. The pathogenetic factors playing a key role in defining the biological features of CLL cells, hence eventually influencing the clinical aggressiveness of the disease, are here divided into "intrinsic factors", mainly genomic alterations of CLL cells, and "extrinsic factors", responsible for direct microenvironmental interactions of CLL cells; the latter group includes interactions of CLL cells occurring via the surface B cell receptor (BCR) and dependent to specific molecular features of the BCR itself and/or to the presence of the BCR-associated molecule ZAP-70, or via other non-BCR-dependent interactions, e.g. specific receptor/ligand interactions, such as CD38/CD31 or CD49d/VCAM-1. A putative final model, discussing the pathogenesis and the clinicobiological features of CLL in relationship of these factors, is also provided.