Intrinsic and extrinsic factors influencing the clinical course of B-cell chronic lymphocytic leukemia: prognostic markers with pathogenetic relevance.
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.
Dal-Bo
Michele
M
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy. micheledalbo@gmail.com
Bertoni
Francesco
F
Forconi
Francesco
F
Zucchetto
Antonella
A
Bomben
Riccardo
R
Marasca
Roberto
R
Deaglio
Silvia
S
Laurenti
Luca
L
Efremov
Dimitar G
DG
Gaidano
Gianluca
G
Del Poeta
Giovanni
G
Gattei
Valter
V
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D002882:Chromosomes, Human, Pair 13; D017353:Gene Deletion; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D011379:Prognosis; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D011947:Receptors, Antigen, B-Cell; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human