{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:23:32Z","timestamp":1784165012986,"version":"3.55.0"},"reference-count":25,"publisher":"American Society of Hematology","issue":"16","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10,19]]},"DOI":"10.1182\/blood.2023019609","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T21:00:21Z","timestamp":1690837221000},"page":"1399-1403","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":8,"title":["Genetic drivers in the natural history of chronic lymphocytic leukemia development as early as 16 years before diagnosis"],"prefix":"10.1182","volume":"142","author":[{"given":"P. Martijn","family":"Kolijn","sequence":"first","affiliation":[{"name":"1Department of Immunology, Laboratory Medical Immunology, Erasmus MC, Rotterdam, The Netherlands"},{"name":"2Division of Environmental Epidemiology and Veterinary Public Health, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-0830","authenticated-orcid":false,"given":"Florentin","family":"Sp\u00e4th","sequence":"additional","affiliation":[{"name":"3Department of Radiation Sciences, Oncology, Cancer Center, Department of Hematology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouhamad","family":"Khouja","sequence":"additional","affiliation":[{"name":"4Second Medical Department, University Hospital Schleswig-Holstein, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0070-138X","authenticated-orcid":false,"given":"Paul J.","family":"Hengeveld","sequence":"additional","affiliation":[{"name":"1Department of Immunology, Laboratory Medical Immunology, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"van der Straten","sequence":"additional","affiliation":[{"name":"1Department of Immunology, Laboratory Medical Immunology, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikos","family":"Darzentas","sequence":"additional","affiliation":[{"name":"5Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Hultdin","sequence":"additional","affiliation":[{"name":"6Department of Medical Biosciences, Pathology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"McKay","sequence":"additional","affiliation":[{"name":"7Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Pott","sequence":"additional","affiliation":[{"name":"4Second Medical Department, University Hospital Schleswig-Holstein, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel C. H.","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"2Division of Environmental Epidemiology and Veterinary Public Health, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-3220","authenticated-orcid":false,"given":"Anton W.","family":"Langerak","sequence":"additional","affiliation":[{"name":"1Department of Immunology, Laboratory Medical Immunology, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"11","key":"2023101915210103900_bib1","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1002\/ajh.25595","article-title":"Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment","volume":"94","author":"Hallek","year":"2019","journal-title":"Am J Hematol"},{"issue":"7","key":"2023101915210103900_bib2","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1056\/NEJMoa0806122","article-title":"B-cell clones as early markers for chronic lymphocytic leukemia","volume":"360","author":"Landgren","year":"2009","journal-title":"N\u00a0Engl J Med"},{"issue":"4","key":"2023101915210103900_bib3","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1182\/blood-2015-02-585059","article-title":"Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic leukemia: diagnosis, natural history, and risk stratification","volume":"126","author":"Strati","year":"2015","journal-title":"Blood"},{"issue":"7","key":"2023101915210103900_bib4","doi-asserted-by":"crossref","first-page":"e67751","DOI":"10.1371\/journal.pone.0067751","article-title":"Combined patterns of IGHV repertoire and cytogenetic\/molecular alterations in monoclonal B lymphocytosis versus chronic lymphocytic leukemia","volume":"8","author":"Henriques","year":"2013","journal-title":"PLoS One"},{"issue":"15","key":"2023101915210103900_bib5","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1182\/blood.2022016279","article-title":"Progression and survival of MBL: a screening study of 10 139 individuals","volume":"140","author":"Slager","year":"2022","journal-title":"Blood"},{"issue":"3","key":"2023101915210103900_bib6","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/leu.2009.287","article-title":"Monoclonal B-cell lymphocytosis (MBL): biology, natural history and clinical management","volume":"24","author":"Shanafelt","year":"2010","journal-title":"Leukemia"},{"issue":"1","key":"2023101915210103900_bib7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/leu.2016.172","article-title":"Genomic characterization of high-count MBL cases indicates that early detection of driver mutations and subclonal expansion are predictors of adverse clinical outcome","volume":"31","author":"Barrio","year":"2017","journal-title":"Leukemia"},{"issue":"12","key":"2023101915210103900_bib8","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1038\/leu.2014.226","article-title":"Monoclonal B-cell lymphocytosis is characterized by mutations in CLL putative driver genes and clonal heterogeneity many years before disease progression","volume":"28","author":"Ojha","year":"2014","journal-title":"Leukemia"},{"issue":"6","key":"2023101915210103900_bib9","doi-asserted-by":"crossref","first-page":"e237","DOI":"10.3324\/haematol.2014.120238","article-title":"Low frequency mutations independently predict poor treatment-free survival in early stage chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis","volume":"100","author":"Winkelmann","year":"2015","journal-title":"Haematologica"},{"issue":"5","key":"2023101915210103900_bib10","doi-asserted-by":"crossref","first-page":"865","DOI":"10.3324\/haematol.2017.177212","article-title":"Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations","volume":"103","author":"Agathangelidis","year":"2018","journal-title":"Haematologica"},{"issue":"15","key":"2023101915210103900_bib11","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1182\/blood.2022017940","article-title":"The clonal evolution and natural history of MBL","volume":"140","author":"Marti","year":"2022","journal-title":"Blood"},{"issue":"7574","key":"2023101915210103900_bib12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nature14666","article-title":"Non-coding recurrent mutations in chronic lymphocytic leukaemia","volume":"526","author":"Puente","year":"2015","journal-title":"Nature"},{"issue":"7574","key":"2023101915210103900_bib13","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nature15395","article-title":"Mutations driving CLL and their evolution in progression and relapse","volume":"526","author":"Landau","year":"2015","journal-title":"Nature"},{"issue":"11","key":"2023101915210103900_bib14","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1038\/s41588-022-01140-w","article-title":"Molecular map of chronic lymphocytic leukemia and its impact on outcome","volume":"54","author":"Knisbacher","year":"2022","journal-title":"Nat Genet"},{"issue":"11","key":"2023101915210103900_bib15","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/s43018-020-00131-2","article-title":"The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome","volume":"1","author":"Duran-Ferrer","year":"2020","journal-title":"Nat Cancer"},{"issue":"10","key":"2023101915210103900_bib16","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1182\/blood.2020007039","article-title":"Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL","volume":"137","author":"Agathangelidis","year":"2021","journal-title":"Blood"},{"issue":"10","key":"2023101915210103900_bib17","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1182\/blood.2021012890","article-title":"High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis","volume":"139","author":"Kolijn","year":"2022","journal-title":"Blood"},{"issue":"16","key":"2023101915210103900_bib18","first-page":"3188","article-title":"Validation of the EuroClonality-NGS DNA capture panel as an integrated genomic tool for lymphoproliferative disorders","volume":"5","author":"Stewart","year":"2021","journal-title":"Blood Adv"},{"issue":"3","key":"2023101915210103900_bib19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41408-022-00650-4","article-title":"Subclonal heterogeneity sheds light on the transformation trajectory in IGLV3-21(R110) chronic lymphocytic leukemia","volume":"12","author":"Paschold","year":"2022","journal-title":"Blood Cancer J"},{"issue":"26","key":"2023101915210103900_bib20","doi-asserted-by":"crossref","first-page":"6904","DOI":"10.1182\/blood-2011-08-373159","article-title":"Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness","volume":"118","author":"Rossi","year":"2011","journal-title":"Blood"},{"issue":"5","key":"2023101915210103900_bib21","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/bjh.12800","article-title":"High-throughput sequencing for the identification of NOTCH1 mutations in early stage chronic lymphocytic leukaemia: biological and clinical implications","volume":"165","author":"Lionetti","year":"2014","journal-title":"Br J Haematol"},{"issue":"7","key":"2023101915210103900_bib22","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1182\/blood.2019000854","article-title":"Prevalence of BTK and PLCG2 mutations in a real-life CLL cohort still on ibrutinib after 3 years: a FILO group study","volume":"134","author":"Quinquenel","year":"2019","journal-title":"Blood"},{"issue":"15","key":"2023101915210103900_bib23","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1182\/blood-2013-10-534271","article-title":"Genetic lesions associated with chronic lymphocytic leukemia chemo-refractoriness","volume":"123","author":"Messina","year":"2014","journal-title":"Blood"},{"issue":"suppl 1","key":"2023101915210103900_bib24","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1182\/blood-2022-169429","article-title":"Autonomous BCR signaling and genetic aberrations in CLL-phenotype monoclonal B lymphocytosis in siblings of CLL patients [abstract]","volume":"140","author":"Sepulveda Yanez","year":"2022","journal-title":"Blood"},{"issue":"8","key":"2023101915210103900_bib25","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1002\/ajh.25831","article-title":"Tumor mutational load predicts time to first treatment in chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis beyond the CLL international prognostic index","volume":"95","author":"Kleinstern","year":"2020","journal-title":"Am J Hematol"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/142\/16\/1399\/2084459\/blood_bld-2023-019609-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/142\/16\/1399\/2084459\/blood_bld-2023-019609-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T15:21:39Z","timestamp":1697728899000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/142\/16\/1399\/497203\/Genetic-drivers-in-the-natural-history-of-chronic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,19]]},"references-count":25,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2023,10,19]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2023019609","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,19]]}}}