CEITEC Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Hematology AP HP Hopital Pitié Salpêtrière UPMC Univ Paris 06 Paris France

Department of Hematology Nikea General Hospital Athens Greece

Department of Immunology Genetics and Pathology Science for Life Laboratory Uppsala University Uppsala Sweden

Department of Immunology Laboratory for Medical Immunology Erasmus MC Rotterdam The Netherlands

Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden

Division of Experimental Oncology IRCCS Istituto Scientifico San Raffaele and Università Vita Salute San Raffaele Milan Italy

IMGT The International ImMunoGeneTics information system Laboratoire d'ImmunoGénétique Moléculaire LIGM Institut de Génétique Humaine IGH UMR CNRS 9002 Université de Montpellier Montpellier France

Institute of Applied Biosciences Center for Research and Technology Hellas Thessaloniki Greece

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Fais F, Ghiotto F, Hashimoto S, Sellars B, Valetto A, Allen SL. Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. J Clin Invest. 1998;102:1515–1525. doi: 10.1172/JCI3009. PubMed DOI PMC

Johnson TA, Rassenti LZ, Kipps TJ. Ig VH1 genes expressed in B cell chronic lymphocytic leukemia exhibit distinctive molecular features. J Immunol. 1997;158:235–246. PubMed

Schroeder HW, Jr, Dighiero G. The pathogenesis of chronic lymphocytic leukemia: analysis of the antibody repertoire. Immunol Today. 1994;15:288–294. doi: 10.1016/0167-5699(94)90009-4. PubMed DOI

Hashimoto S, Dono M, Wakai M, Allen SL, Lichtman SM, Schulman P. Somatic diversification and selection of immunoglobulin heavy and light chain variable region genes in IgG+ CD5+ chronic lymphocytic leukemia B cells. J Exp Med. 1995;181:1507–1517. doi: 10.1084/jem.181.4.1507. PubMed DOI PMC

Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94:1840–1847. PubMed

Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94:1848–1854. PubMed

Vardi A, Agathangelidis A, Sutton LA, Ghia P, Rosenquist R, Stamatopoulos K. Immunogenetic studies of chronic lymphocytic leukemia: revelations and speculations about ontogeny and clinical evolution. Cancer Res. 2014;74:4211–4216. doi: 10.1158/0008-5472.CAN-14-0630. PubMed DOI

Burger JA, Chiorazzi N. B cell receptor signaling in chronic lymphocytic leukemia. Trends Immunol. 2013;34:592–601. doi: 10.1016/j.it.2013.07.002. PubMed DOI PMC

Packham G, Krysov S, Allen A, Savelyeva N, Steele AJ, Forconi F. The outcome of B-cell receptor signaling in chronic lymphocytic leukemia: proliferation or anergy. Haematologica. 2014;99:1138–1148. doi: 10.3324/haematol.2013.098384. PubMed DOI PMC

Sutton LA, Rosenquist R. The complex interplay between cell-intrinsic and cell-extrinsic factors driving the evolution of chronic lymphocytic leukemia. Semin Cancer Biol. 2015;34:22–35. doi: 10.1016/j.semcancer.2015.04.009. PubMed DOI

Agathangelidis A, Darzentas N, Hadzidimitriou A, Brochet X, Murray F, Yan XJ. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. Blood. 2012;119:4467–4475. doi: 10.1182/blood-2011-11-393694. PubMed DOI PMC

Messmer BT, Albesiano E, Efremov DG, Ghiotto F, Allen SL, Kolitz J. Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia. J Exp Med. 2004;200:519–525. doi: 10.1084/jem.20040544. PubMed DOI PMC

Stamatopoulos K, Belessi C, Moreno C, Boudjograh M, Guida G, Smilevska T. Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations. Blood. 2007;109:259–270. doi: 10.1182/blood-2006-03-012948. PubMed DOI

Gounari M, Ntoufa S, Apollonio B, Papakonstantinou N, Ponzoni M, Chu CC. Excessive antigen reactivity may underlie the clinical aggressiveness of chronic lymphocytic leukemia stereotyped subset #8. Blood. 2015;125:3580–3587. doi: 10.1182/blood-2014-09-603217. PubMed DOI PMC

Ntoufa S, Papakonstantinou N, Apollonio B, Gounari M, Galigalidou C, Fonte E. B cell anergy modulated by TLR1/2 and the miR-17 approximately 92 cluster underlies the indolent clinical course of chronic lymphocytic leukemia stereotyped subset #4. J Immunol. 2016;196:4410–4417. doi: 10.4049/jimmunol.1502297. PubMed DOI

Mansouri L, Sutton LA, Ljungstrom V, Bondza S, Arngarden L, Bhoi S. Functional loss of IkappaBepsilon leads to NF-kappaB deregulation in aggressive chronic lymphocytic leukemia. J Exp Med. 2015;212:833–843. doi: 10.1084/jem.20142009. PubMed DOI PMC

Navrkalova V, Young E, Baliakas P, Radova L, Sutton LA, Plevova K. ATM mutations in major stereotyped subsets of chronic lymphocytic leukemia: enrichment in subset #2 is associated with markedly short telomeres. Haematologica. 2016;101:e369–e373. doi: 10.3324/haematol.2016.142968. PubMed DOI PMC

Rossi D, Spina V, Bomben R, Rasi S, Dal-Bo M, Bruscaggin A. Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia. Blood. 2013;121:4902–4905. doi: 10.1182/blood-2013-02-486209. PubMed DOI

Sutton LA, Young E, Baliakas P, Hadzidimitriou A, Moysiadis T, Plevova K. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors. Haematologica. 2016;101:959–967. doi: 10.3324/haematol.2016.141812. PubMed DOI PMC

Baliakas P, Hadzidimitriou A, Sutton LA, Minga E, Agathangelidis A, Nichelatti M. Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study. Lancet Haematol. 2014;1:e74–e84. doi: 10.1016/S2352-3026(14)00005-2. PubMed DOI

Stamatopoulos K, Agathangelidis A, Rosenquist R, Ghia P. Antigen receptor stereotypy in chronic lymphocytic leukemia. Leukemia. 2017;31:282–291. doi: 10.1038/leu.2016.322. PubMed DOI

Strefford JC, Sutton LA, Baliakas P, Agathangelidis A, Malcikova J, Plevova K. Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: the case of SF3B1 and subset #2. Leukemia. 2013;27:2196–2199. doi: 10.1038/leu.2013.98. PubMed DOI

Baliakas P, Agathangelidis A, Hadzidimitriou A, Sutton LA, Minga E, Tsanousa A. Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations. Blood. 2015;125:856–859. doi: 10.1182/blood-2014-09-600874. PubMed DOI PMC

Fischer K, Bahlo J, Fink AM, Goede V, Herling CD, Cramer P. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127:208–215. doi: 10.1182/blood-2015-06-651125. PubMed DOI

Rossi D, Terzi-di-Bergamo L, De Paoli L, Cerri M, Ghilardi G, Chiarenza A et al. Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia. Blood126: 1921–1924. PubMed PMC

Thompson PA, Tam CS, O'Brien SM, Wierda WG, Stingo F, Plunkett W. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood. 2016;127:303–309. doi: 10.1182/blood-2015-09-667675. PubMed DOI PMC

Ghia P, Stamatopoulos K, Belessi C, Moreno C, Stilgenbauer S, Stevenson F. ERIC recommendations on IGHV gene mutational status analysis in chronic lymphocytic leukemia. Leukemia. 2007;21:1–3. doi: 10.1038/sj.leu.2404457. PubMed DOI

Langerak AW, Davi F, Ghia P, Hadzidimitriou A, Murray F, Potter KN. Immunoglobulin sequence analysis and prognostication in CLL: guidelines from the ERIC review board for reliable interpretation of problematic cases. Leukemia. 2011;25:979–984. doi: 10.1038/leu.2011.49. PubMed DOI

Bystry V, Agathangelidis A, Bikos V, Sutton LA, Baliakas P, Hadzidimitriou A. ARResT/AssignSubsets: a novel application for robust subclassification of chronic lymphocytic leukemia based on B cell receptor IG stereotypy. Bioinformatics. 2015;31:3844–3846. PubMed

Belessi CJ, Davi FB, Stamatopoulos KE, Degano M, Andreou TM, Moreno C. IGHV gene insertions and deletions in chronic lymphocytic leukemia: ‘CLL-biased’ deletions in a subset of cases with stereotyped receptors. Eur J Immunol. 2006;36:1963–1974. doi: 10.1002/eji.200535751. PubMed DOI

Davis Z, Forconi F, Parker A, Gardiner A, Thomas P, Catovsky D. The outcome of chronic lymphocytic leukaemia patients with 97% IGHV gene identity to germline is distinct from cases with <97% identity and similar to those with 98% identity. Br J Haematol. 2016;173:127–136. doi: 10.1111/bjh.13940. PubMed DOI

Sanchez ML, Almeida J, Gonzalez D, Gonzalez M, Garcia-Marcos MA, Balanzategui A. Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone. Blood. 2003;102:2994–3002. doi: 10.1182/blood-2003-01-0045. PubMed DOI

Realizing precision medicine in chronic lymphocytic leukemia: Remaining challenges and potential opportunities

Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

The EHA Research Roadmap: Malignant Lymphoid Diseases

Consistent B Cell Receptor Immunoglobulin Features Between Siblings in Familial Chronic Lymphocytic Leukemia

Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL

Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study

European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms

No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy