@article{3001712,
    title = "Not all IGHV3-21 chronic lymphocytic leukemias are equal: Prognostic considerations",
    author = "Baliakas, P. and Agathangelidis, A. and Hadzidimitriou, A. and Sutton, L.-A. and Minga, E. and Tsanousa, A. and Scarfò, L. and Davis, Z. and Yan, X.-J. and Shanafelt, T. and Plevova, K. and Sandberg, Y. and Vojdeman, F.J. and Boudjogra, M. and Tzenou, T. and Chatzouli, M. and Chu, C.C. and Veronese, S. and Gardiner, A. and Mansouri, L. and Smedby, K.E. and Pedersen, L.B. and Moreno, D. and Van Lom, K. and Giudicelli, V. and Francova, H.S. and Nguyen-Khac, F. and Panagiotidis, P. and Juliusson, G. and Angelis, L. and Anagnostopoulos, A. and Lefranc, M.-P. and Facco, M. and Trentin, L. and Catherwood, M. and Montillo, M. and Geisler, C.H. and Langerak, A.W. and Pospisilova, S. and Chiorazzi, N. and Oscier, D. and Jelinek, D.F. and Darzentas, N. and Belessi, C. and Davi, F. and Ghia, P. and Rosenquist, R. and Stamatopoulos, K.",
    journal = "Blood advances",
    year = "2015",
    volume = "125",
    number = "5",
    pages = "856-859",
    publisher = "American Society of Hematology",
    doi = "10.1182/blood-2014-09-600874",
    keywords = "adult;  adult;  amino acid composition;  amino acid composition;  Article;  cancer patient;  cancer patient;  cancer prognosis;  cancer prognosis;  chronic lymphatic leukemia;  chronic lymphatic leukemia;  female;  female;  gene mutation;  gene mutation;  human;  human;  IGHV3 21 gene;  IGHV3 21 gene;  in situ hybridization;  in situ hybridization;  major clinical study;  major clinical study;  male;  male;  priority journal;  priority journal;  prospective study;  prospective study;  tumor gene;  tumor gene;  aged;  B lymphocyte;  drug effects;  gene expression regulation;  gene rearrangement;  genetic heterogeneity;  genetics;  immunology;  Leukemia, Lymphocytic, Chronic, B-Cell;  middle aged;  mortality;  pathology;  prognosis;  somatic hypermutation;  survival analysis;  time to treatment;  treatment outcome, antineoplastic agent;  immunoglobulin heavy chain, Aged;  Antineoplastic Agents;  B-Lymphocytes;  Female;  Gene Expression Regulation, Leukemic;  Gene Rearrangement, B-Lymphocyte, Heavy Chain;  Genetic Heterogeneity;  Humans;  Immunoglobulin Heavy Chains;  Leukemia, Lymphocytic, Chronic, B-Cell;  Male;  Middle Aged;  Prognosis;  Somatic Hypermutation, Immunoglobulin;  Survival Analysis;  Time-to-Treatment;  Treatment Outcome",
    abstract = "An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2.Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL. © 2015 by The American Society of Hematology 10.1182/blood-2014-09-600874."
}