Originally published as JCO Early Release 10.1200/JCO.2007.15.4393 on July 28 2008

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Caligaris-Cappio, F. Articles by Ghia, P. Search for Related Content PubMed PubMed Citation Articles by Caligaris-Cappio, F. Articles by Ghia, P. Social Bookmarking                            What's this?

Novel Insights in Chronic Lymphocytic Leukemia: Are We Getting Closer to Understanding the Pathogenesis of the Disease?

Federico Caligaris-Cappio, Paolo Ghia

From the Unit and Laboratory of Lymphoid Malignancies, Department of Oncology, Università Vita-Salute San Raffaele and Istituto Scientifico San Raffaele, Milano, Italy

Corresponding author: Federico Caligaris-Cappio, MD, Department of Oncology, Istituto Scientifico San Raffaele, Via Olgettina 60, 20132, Milano, Italy; e-mail: caligaris.federico{at}hsr.it

Chronic lymphocytic leukemia (CLL) has unique epidemiologic, biologic, and clinical features. The progressively emerging picture leads us to consider that the critical genes for malignant CLL cells are those regulated by a number of microRNAs revealed by refined cytogenetic and molecular studies, and that the key molecule is the B-cell receptor (BCR). The hypothesis that CLL cells might be selected by some sort of antigenic pressure is strengthened by numerous findings indicating that a BCR-mediated stimulation plays a relevant role in the natural history of the disease and that autoantigens, as well as molecular structures instrumental in eliminating and scavenging apoptotic cells and pathogenic bacteria, may be relevant in triggering and/or facilitating the evolution of CLL. An important question is whether the tiny monoclonal B-cell populations phenotypically similar to CLL (that occur in the peripheral blood of about 3.5% of healthy individuals and are termed monoclonal B lymphocytosis) might be a critical step in the development of CLL. All relevant events of CLL occur in tissues in which a number of cellular and molecular interactions shape a microenvironment conducive to the accumulation of malignant cells and favor the organization of proliferating cells in focal aggregates of variable size that form the pseudofollicular proliferation centers. Given the impact that understanding the pathogenesis of CLL might have on the development of new treatments, the purposes of this review are to discuss whether the novel insights in CLL are leading us closer to understanding the tenet of the disease; to define the emerging new, stimulating questions; and to unfold the major challenges that still need to be addressed.

published online ahead of print at www.jco.org on July 28, 2008.

Supported by the Associazione Italiana per la Ricerca sul Cancro (Milan), the CLL Global Research Foundation (Houston, TX), Programma di Ricerca Scientifica di Rilevanza Nazionale, Sostegno alla Ricerca di Base, and Progetto Integrato Oncologia.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				D. Rossi, V. Spina, M. Cerri, S. Rasi, C. Deambrogi, L. De Paoli, L. Laurenti, R. Maffei, F. Forconi, F. Bertoni, et al. Stereotyped B-Cell Receptor Is an Independent Risk Factor of Chronic Lymphocytic Leukemia Transformation to Richter Syndrome Clin. Cancer Res., July 1, 2009; 15(13): 4415 - 4422. [Abstract] [Full Text] [PDF]

				S. Deaglio and F. Malavasi Chronic lymphocytic leukemia microenvironment: shifting the balance from apoptosis to proliferation Haematologica, June 1, 2009; 94(6): 752 - 756. [Full Text] [PDF]

				F. Caligaris-Cappio ROMA illuminates CLL genomic lesions Blood, February 5, 2009; 113(6): 1209 - 1210. [Full Text] [PDF]

				J. Gordon Dis-Abl-ing CD40 buys toxic assets Blood, December 15, 2008; 112(13): 4787 - 4788. [Full Text] [PDF]