Event Abstract Back to Event Significance of immunoglobulin B-cell receptor features in tumor dynamics of chronic lymphocytic leukemia Karla Plevova1, 2*, Hana Skuhrova Francova1, Kamila Brazdilova1, 2, Sarka Pavlova1, 2, Katerina Burckova1, Michael Doubek1, 2, Yvona Brychtova1, Boris Tichy1, 2 and Sarka Pospisilova1, 2 1 University Hospital Brno, Department of Internal Medicine - Hematology and Oncology, Czechia 2 Central European Institute of Technology, Masaryk University, Czechia Chronic lymphocytic leukemia (CLL) is a malignant lymphoproliferative disorder characterized by monoclonal expansion of mature B-cells. Presence/absence of somatic hypermutations in clonal heavy chain immunoglobulin gene (IGH), specifically its variable region IGHV, represents a crucial prognostic marker stratifying patients into subgroups with different clinical outcome. Sporadically, cases with multiple IGHs are observed. From clinical point of view, they preclude conclusive prognostic interpretation. However, they constitute a remarkable model of CLL tumorigenesis. Thus, we investigated biological cause of the multiple IGHs and over-time clone behavior in 31 CLL patients with respect to molecular features of B-cell receptor. We identified definite co-existence of two clonal B-cell populations with different light chain restriction (9/31 cases), or highly likely co-existence of two or more independent clones with homogenous phenotype (16/31 cases). In cases with consecutive samples, we performed quantitative evaluation of over-time changes in clone proportions. Interestingly, we observed clonal drifts, mainly diminishing of a clone (18 cases) but also appearing of a new one (3 cases). Clones with specific immunogenetic features of IGH, namely (i) higher IGHV identity to germ-line and/or (i) longer HCDR3, were preferred during the disease evolution. Significantly, these clone characteristics are important markers of clinical outcome. Our study allowed novel insight into biological causes of multiple IGH detection in CLL, typically monoclonal disease. Importantly, we observed clonal drift favoring specific molecular B cell receptor features, which might eventually provide further insight into disease evolution with implications for patient monitoring and therapy. Acknowledgements Supported by Sylica project 286154, NT13493-4/2012, CZ.1.07/2.4.00/17.0042, MUNI/A/0723/2012, DRO FNBr 65269705, CZ.1.05/1.1.00/02.0068, MSM0021622430. References Langerak AW, Davi F, Ghia P, Hadzidimitriou A, Murray F, Potter KN, et al. Immunoglobulin sequence analysis and prognostication in CLL: guidelines from the ERIC review board for reliable interpretation of problematic cases. Leukemia. 2011;25(6):979-84. Rassenti LZ, Kipps TJ. Lack of allelic exclusion in B cell chronic lymphocytic leukemia. J Exp Med. 1997;185(8):1435-45. Sanchez ML, Almeida J, Gonzalez D, Gonzalez M, Garcia-Marcos MA, Balanzategui A, et al. Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone. Blood. 2003;102(8):2994-3002. Keywords: chronic lymphocytic leukemia, B cell receptor, Immunoglobulin gene, double productive IGH rearrangement, biclonal leukemia Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune receptors and signaling Citation: Plevova K, Skuhrova Francova H, Brazdilova K, Pavlova S, Burckova K, Doubek M, Brychtova Y, Tichy B and Pospisilova S (2013). Significance of immunoglobulin B-cell receptor features in tumor dynamics of chronic lymphocytic leukemia. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01069 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Mrs. Karla Plevova, University Hospital Brno, Department of Internal Medicine - Hematology and Oncology, Brno, 61300, Czechia, karla.plevova@mail.muni.cz Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Karla Plevova Hana Skuhrova Francova Kamila Brazdilova Sarka Pavlova Katerina Burckova Michael Doubek Yvona Brychtova Boris Tichy Sarka Pospisilova Google Karla Plevova Hana Skuhrova Francova Kamila Brazdilova Sarka Pavlova Katerina Burckova Michael Doubek Yvona Brychtova Boris Tichy Sarka Pospisilova Google Scholar Karla Plevova Hana Skuhrova Francova Kamila Brazdilova Sarka Pavlova Katerina Burckova Michael Doubek Yvona Brychtova Boris Tichy Sarka Pospisilova PubMed Karla Plevova Hana Skuhrova Francova Kamila Brazdilova Sarka Pavlova Katerina Burckova Michael Doubek Yvona Brychtova Boris Tichy Sarka Pospisilova Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.