title: Stereotyped B-cell receptors in chronic lymphocytic leukemia.
abstract: Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IGs) has proved to be a particularly fruitful field in chronic lymphocytic leukemia (CLL), not only for understanding disease pathogenesis but also for discriminating clinical subgroups with markedly distinct course and outcome. Of utmost importance was the identification of quasi-identical BcR IGs among unrelated patients with CLL, fittingly coined as "stereotypy," that set the wheels in motion for unraveling the role of antigen(s) in the selection and expansion of the leukemic clones. The categorization of CLL clones into "subsets" according to shared BcR IG structural characteristics provided a compartmentalized view of this otherwise heterogeneous disease, which eventually led to defining strikingly homogeneous groups of patients in terms of: (i) functional properties of the clonal BcR IGs, e.g. BcR reactivity and signaling; (ii) clonal genetic landscape, e.g. genomic aberrations, gene expression/methylation profiles, microRNA signatures; and (iii) clinical course and outcome. The remarkable restriction of the CLL IG gene repertoire, resulting to a great degree from the high impact of BcR IG stereotypy, may also prompt speculations regarding CLL ontogenesis. Overall, the BcR IG molecule justifiably lies at the heart of CLL clinical research, holding the promise of subset-tailored therapies.
authors.affiliation: Division of Molecular Oncology, San Raffaele Scientific Institute , Milan , Italy.
authors.forename: Andreas
authors.initials: A
authors.lastname: Agathangelidis
authors.forename: Anna
authors.initials: A
authors.lastname: Vardi
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Baliakas
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D060965:Clonal Evolution; D019175:DNA Methylation; D015973:Gene Expression Regulation, Leukemic; D014644:Genetic Variation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000941:Antigens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D035683:MicroRNAs; D011947:Receptors, Antigen, B-Cell
keywords: B-cell receptors; BcR IG; chronic lymphocytic leukemia