Antigen receptor stereotypy in chronic lymphocytic leukemia.
The discovery of almost identical or 'stereotyped' B-cell receptor immunoglobulins (BcR IG) among unrelated patients with chronic lymphocytic leukemia (CLL) cemented the idea of antigen selection in disease ontogeny and evolution. The systematic analysis of the stereotypy phenomenon in CLL revealed that around one-third of CLL patients may be grouped into subsets based on shared sequence motifs within the variable heavy complementarity determining region 3. Stereotyped subsets display a strikingly similar biology of the leukemic clones, referring to many different levels, from the immunogenetic and genetic and extending to the epigenetic and functional levels. Even more importantly, the homogeneity of stereotyped subsets has clinical consequences as patients assigned to the same stereotyped subset generally exhibit an overall similar disease course and outcome. In other words, stereotypy-based patient classification of CLL has already provided a more compartmentalized view of this otherwise heterogeneous disease and can assist in refining prognostication models. While this is relevant only for the one-third of cases expressing stereotyped BcR IG; in principle, however, the findings from further analysis of the stereotyped subsets may also contribute towards improved understanding of the remaining non-stereotyped fraction of CLL patients.
Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece.|Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
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Stamatopoulos
Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece.|Division of Experimental Oncology and Department of Onco-Hematology, Università Vita-Salute San Raffaele and IRCCS San Raffaele Scientific Institute Milano, Milano, Italy.
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Agathangelidis
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
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Rosenquist
Division of Experimental Oncology and Department of Onco-Hematology, Università Vita-Salute San Raffaele and IRCCS San Raffaele Scientific Institute Milano, Milano, Italy.
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Ghia
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D018740:Genetic Heterogeneity; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D011379:Prognosis; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000378:metabolism*; D027041:Somatic Hypermutation, Immunoglobulin
D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D011947:Receptors, Antigen, B-Cell