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Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies by Andreas Agathangelidis, Nikos Darzentas, Anastasia Hadzidimitriou, Xavier Brochet, Fiona Murray, Xiao-Jie Yan, Zadie Davis, Ellen J. van Gastel-Mol, Cristina Tresoldi, Charles C. Chu, Nicola Cahill, Veronique Giudicelli, Boris Tichy, Lone Bredo Pedersen, Letizia Foroni, Lisa Bonello, Agnieszka Janus, Karin Smedby, Achilles Anagnostopoulos, Helene Merle-Beral, Nikolaos Laoutaris, Gunnar Juliusson, Paola Francia di Celle, Sarka Pospisilova, Jesper Jurlander, Christian Geisler, Athanasios Tsaftaris, Marie-Paule Lefranc, Anton W. Langerak, David Graham Oscier, Nicholas Chiorazzi, Chrysoula Belessi, Frederic Davi, Richard Rosenquist, Paolo Ghia, and Kostas Stamatopoulos Blood Volume 119(19):4467-4475 May 10, 2012 ©2012 by American Society of Hematology A limited number of major subsets accounts for a sizeable proportion of the CLL Ig repertoire. Andreas Agathangelidis et al. Blood 2012;119:4467-4475 ©2012 by American Society of Hematology Sequence logos of selected major subsets in CLL. (A) Subset 6 comprises 68 unmutated IGHV169/IGHD3-16/IGHJ3 rearrangements, characterized by pronounced overall similarity. Andreas Agathangelidis et al. Blood 2012;119:4467-4475 ©2012 by American Society of Hematology Two types of subset-defining VH CDR3 sequence patterns. Andreas Agathangelidis et al. Blood 2012;119:4467-4475 ©2012 by American Society of Hematology Stereotypes in CLL are disease-biased. Andreas Agathangelidis et al. Blood 2012;119:4467-4475 ©2012 by American Society of Hematology CLL Ig repertoire: one-third stereotyped, two-thirds heterogeneous. Andreas Agathangelidis et al. Blood 2012;119:4467-4475 ©2012 by American Society of Hematology Intriguing sequence similarities between different high-level subsets. Andreas Agathangelidis et al. Blood 2012;119:4467-4475 ©2012 by American Society of Hematology