A B-cell epigenetic signature defines three biologic subgroups of chronic lymphocytic leukemia with clinical impact (original) (raw)
References
- Rozman C, Montserrat E . Chronic lymphocytic leukemia. NEngl J Med 1995; 333: 1052–1057.
Article CAS Google Scholar - Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999; 94: 1840–1847.
CAS PubMed Google Scholar - 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.
CAS PubMed Google Scholar - Chiorazzi N, Ferrarini M . Cellular origin(s) of chronic lymphocytic leukemia: cautionary notes and additional considerations and possibilities. Blood 2011; 117: 1781–1791.
Article CAS PubMed PubMed Central Google Scholar - Kulis M, Heath S, Bibikova M, Queiros AC, Navarro A, Clot G et al. Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia. Nat Genet 2012; 44: 1236–1242.
Article CAS PubMed Google Scholar - Seifert M, Sellmann L, Bloehdorn J, Wein F, Stilgenbauer S, Durig J et al. Cellular origin and pathophysiology of chronic lymphocytic leukemia. J Exp Med 2012; 209: 2183–2198.
Article CAS PubMed PubMed Central Google Scholar - Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003; 348: 1764–1775.
Article CAS PubMed Google Scholar - Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000; 343: 1910–1916.
Article CAS PubMed Google Scholar - Fabbri G, Rasi S, Rossi D, Trifonov V, Khiabanian H, Ma J et al. Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med 2011; 208: 1389–1401.
Article CAS PubMed PubMed Central Google Scholar - Puente XS, Pinyol M, Quesada V, Conde L, Ordonez GR, Villamor N et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 2011; 475: 101–105.
Article CAS PubMed PubMed Central Google Scholar - Quesada V, Conde L, Villamor N, Ordonez GR, Jares P, Bassaganyas L et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 2012; 44: 47–52.
Article CAS Google Scholar - Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011; 365: 2497–2506.
Article CAS PubMed PubMed Central Google Scholar - Rossi D, Rasi S, Spina V, Bruscaggin A, Monti S, Ciardullo C et al. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood 2013; 121: 1403–1412.
Article CAS PubMed PubMed Central Google Scholar - Baylin SB, Jones PA . A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer 2011; 11: 726–734.
Article CAS PubMed PubMed Central Google Scholar - Esteller M . Epigenetics in cancer. N Engl J Med 2008; 358: 1148–1159.
Article CAS PubMed Google Scholar - Heyn H, Esteller M . DNA methylation profiling in the clinic: applications and challenges. Nat Rev 2012; 13: 679–692.
Article CAS Google Scholar - Bird A . DNA methylation patterns and epigenetic memory. Genes Dev 2002; 16: 6–21.
Article CAS PubMed Google Scholar - Bird A . Perceptions of epigenetics. Nature 2007; 447: 396–398.
Article CAS PubMed Google Scholar - Du P, Zhang X, Huang CC, Jafari N, Kibbe WA, Hou L et al. Comparison of beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinform 2010; 11: 587.
Article CAS Google Scholar - Efron B, Tibshirani RJ . Improvements on cross-validation: the 632+ bootstrap method. J Am Stat Assoc 1997; 92: 548–560.
Google Scholar - Cortes C, Vapnik V . Support-vector networks. Mach Learn 1995; 20: 273–297.
Google Scholar - Tost J, Gut IG . DNA methylation analysis by pyrosequencing. Nat Protoc 2007; 2: 2265–2275.
Article CAS PubMed Google Scholar - Lamprecht B, Walter K, Kreher S, Kumar R, Hummel M, Lenze D et al. Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nat Med 2010; 16: 571–579.
Article CAS PubMed Google Scholar - Cheson BD, Bennett JM, Rai KR, Grever MR, Kay NE, Schiffer CA et al. Guidelines for clinical protocols for chronic lymphocytic leukemia: recommendations of the National Cancer Institute-sponsored working group. Am J Hematol 1988; 29: 152–163.
Article CAS PubMed Google Scholar - Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990–4997.
CAS PubMed Google Scholar - Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111: 5446–5456.
Article CAS PubMed PubMed Central Google Scholar - Kaplan EL, Meier P . Non parametric estimation from incomplete observation. J Am Stat Assoc 1958; 53: 457–481.
Article Google Scholar - Peto R, Pike MC . Conservatism of the approximation sigma (O-E)2-E in the logrank test for survival data or tumor incidence data. Biometrics 1973; 29: 579–584.
Article CAS PubMed Google Scholar - Cox DR . Regression models and life tables. J R Stat Soc Ser B 1972; 34: 187–220.
Google Scholar - Klein JP, Moeschberger ML . Survival Analysis. Techniques for Censored and Truncated Data. Springer: New York, NY, USA, 1997.
Google Scholar - Laird PW . The power and the promise of DNA methylation markers. Nat Rev Cancer 2003; 3: 253–266.
Article CAS PubMed Google Scholar - Rodriguez-Paredes M, Esteller M . Cancer epigenetics reaches mainstream oncology. Nat Med 2011; 17: 330–339.
Article CAS PubMed Google Scholar - Fernandez AF, Assenov Y, Martin-Subero JI, Balint B, Siebert R, Taniguchi H et al. A DNA methylation fingerprint of 1628 human samples. Genome Res 2012; 22: 407–419.
Article CAS PubMed PubMed Central Google Scholar - Gaidano G, Foa R, Dalla-Favera R . Molecular pathogenesis of chronic lymphocytic leukemia. J Clin Invest 2012; 122: 3432–3438.
Article CAS PubMed PubMed Central Google Scholar - Berkowska MA, Driessen GJ, Bikos V, Grosserichter-Wagener C, Stamatopoulos K, Cerutti A et al. Human memory B cells originate from three distinct germinal center-dependent and -independent maturation pathways. Blood 2011; 118: 2150–2158.
Article CAS PubMed PubMed Central Google Scholar - Cerutti A, Cols M, Puga I . Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. Nat Rev Immunol 2013; 13: 118–132.
Article CAS PubMed PubMed Central Google Scholar - Strefford JC, Sutton LA, Baliakas P, Agathangelidis A, Malcikova J, Plevova K et al. 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.
Article CAS PubMed Google Scholar - Zenz T, Mertens D, Kuppers R, Dohner H, Stilgenbauer S . From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer 2010; 10: 37–50.
Article CAS PubMed Google Scholar - Abrisqueta P, Pereira A, Rozman C, Aymerich M, Gine E, Moreno C et al. Improving survival in patients with chronic lymphocytic leukemia (1980-2008): the Hospital Clinic of Barcelona experience. Blood 2009; 114: 2044–2050.
Article CAS PubMed Google Scholar
Acknowledgements
We are grateful to S Guijarro, S Martín, C Capdevila, M Sánchez, L Plà, A Heydorn and G Riesen for excellent technical assistance, and to N Villahoz and C Muro for excellent work in the coordination of the Spanish CLL Genome Consortium. We are indebted to the Hospital Clínic de Barcelona–IDIBAPS Biobank-Tumor Bank and Hematopathology Collection for the sample procurement as well as to the technical and medical staff of all the laboratories involved in the study. We are also very grateful to the patients with CLL who have participated in this study. This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through the Instituto de Salud Carlos III (ISCIII) and the Red Temática de Investigación del Cáncer (RTICC) of the ISCIII (RD12/0036/0036 to EC, RD12/0036/0023 to AL-G, RD12/0036/0004 to DC and RD12/0036/0067 to CL-O) and project SAF2009-08663 (JIM-S), the UK Medical Research Council (AM, SJ and MJSD) as well as the European Union’s Seventh Framework Programme through the Blueprint Consortium (grant agreement 282510 to EC and RS). CL-O is a researcher of the Botín Foundation and EC an ICREA-Academia researcher. JIM-S is supported by a Ramon y Cajal contract of the MINECO, ACQ by the Portuguese Fundação para a Ciência e a Tecnologia, MK by the Agència de Gestió d’Ajuts Universitaris i de Recerca (Generalitat de Catalunya) and JR by a Junior Excellence Research Group of the Jackstädt foundation.
Author Contributions
ACQ, MK, AN, JR, AKB, JK, CR, NR and ML-G performed experiments. ACQ, NV, AM-T, G Clot, G Castellano, SB, IS, XSP, RS, CR, AL-G and JIM-S analyzed and interpreted data. EMM-P, MP and MA performed sample preparation and quality control. NV, AM-T, SJ, AM, DC, MA, MR, JD, EG, MG-D and MJSD reviewed the pathologic and clinical data and confirmed diagnosis. CL-O, EC and JIM-S designed the study. ACQ, NV, EC, AL-G and JIM-S wrote the manuscript. All authors read and approved the final version of the manuscript.
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Author notes
- A C Queirós and N Villamor: These authors contributed equally to this study as first authors.
- A López-Guillermo and J I Martín-Subero: These authors contributed equally to this study as senior authors.
Authors and Affiliations
- Departamento de Anatomía Patológica, Unidad de Hematopatología, Servicio de Anatomía Patológica, Hospital Clínic, Farmacología y Microbiología, Universitat de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
A C Queirós, N Villamor, G Clot, M Kulis, A Navarro, C Royo, N Russiñol, G Castellano, M Pinyol, S Bea, I Salaverria, M López-Guerra, D Colomer, M Aymerich, M Rozman, E Campo & J I Martín-Subero - Servicio de Hematología, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain
A Martinez-Trillos, J Delgado, E Giné & A López-Guillermo - Institute of Human Genetics, Christian-Albrechts-University of Kiel, University Hospital Schleswig-Holstein, Campus Kiel, Germany
E M M Penas, J Richter, A K Bergmann, J Kolarova & R Siebert - MRC Toxicology Unit Leicester, Leicester, UK
S Jayne & A Majid - Servicio de Hematología, Hospital Universitario, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Universidad de Salamanca, Salamanca, Spain,
M González-Díaz - Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain
X S Puente & C López-Otín - Ernest and Helen Scott Haematological Research Institute, Leicester University, Leicester, UK
M J S Dyer - Josep Carreras Leukemia Research Institute, Barcelona, Spain
C Rozman
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Queirós, A., Villamor, N., Clot, G. et al. A B-cell epigenetic signature defines three biologic subgroups of chronic lymphocytic leukemia with clinical impact.Leukemia 29, 598–605 (2015). https://doi.org/10.1038/leu.2014.252
- Received: 14 January 2014
- Revised: 01 August 2014
- Accepted: 11 August 2014
- Published: 25 August 2014
- Issue Date: March 2015
- DOI: https://doi.org/10.1038/leu.2014.252