{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:03:29Z","timestamp":1793916209605,"version":"4.8.0"},"reference-count":24,"publisher":"American Society of Hematology","issue":"17","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"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":[[2024,4,25]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Monoclonal B-cell lymphocytosis (MBL) progresses to chronic lymphocytic leukemia (CLL) requiring therapy at 1% to 5% per year. Improved prediction of progression would greatly benefit individuals with MBL. Patients with CLL separate into 3 distinct epigenetic subtypes (epitypes) with high prognostic significance, and recently the intermediate epitype has been shown to be enriched for high-risk immunoglobulin lambda variable (IGLV) 3-21 rearrangements, impacting outcomes for these patients. Here, we employed this combined strategy to generate the epigenetic and light chain immunoglobulin (ELCLV3-21) signature to classify 219 individuals with MBL. The ELCLV3-21 high-risk signature distinguished MBL individuals with a high probability of progression (39.9% and 71.1% at 5 and 10 years, respectively). ELCLV3-21 improved the accuracy of predicting time to therapy for individuals with MBL compared with other established prognostic indicators, including the CLL international prognostic index (c-statistic, 0.767 vs 0.668, respectively). Comparing ELCLV3-21 risk groups in MBL vs a cohort of 226 patients with CLL revealed ELCLV3-21 high-risk individuals with MBL had significantly shorter time to therapy (P\u00a0= .003) and reduced overall survival (P\u00a0= .03) compared with ELCLV3-21 low-risk individuals with CLL. These results highlight the power of the ELCLV3-21 approach to identify individuals with a higher likelihood of adverse clinical outcome and may provide a more accurate approach to classify individuals with small B-cell clones.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023022180","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T22:15:52Z","timestamp":1704838552000},"page":"1752-1757","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":13,"title":["Prediction of outcomes for high-count monoclonal B\u00a0lymphocytosis using an epigenetic and immunogenetic signature"],"prefix":"10.1182","volume":"143","author":[{"given":"Salma B.","family":"Abdelbaky","sequence":"first","affiliation":[{"name":"1Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH"},{"name":"2The Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Giacopelli","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH"},{"name":"2The Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7313-1875","authenticated-orcid":false,"given":"Kari G.","family":"Rabe","sequence":"additional","affiliation":[{"name":"3Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9746-3563","authenticated-orcid":false,"given":"Kyoko","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH"},{"name":"2The Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Zhong","family":"Wu","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH"},{"name":"2The Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihuang","family":"Yan","sequence":"additional","affiliation":[{"name":"4Division of Computational Biology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tait D.","family":"Shanafelt","sequence":"additional","affiliation":[{"name":"5Division of Hematology, Department of Medicine, Stanford University, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-7314","authenticated-orcid":false,"given":"Sameer A.","family":"Parikh","sequence":"additional","affiliation":[{"name":"6Division of Hematology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ding","sequence":"additional","affiliation":[{"name":"6Division of Hematology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1292-3024","authenticated-orcid":false,"given":"Paul J.","family":"Hampel","sequence":"additional","affiliation":[{"name":"6Division of Hematology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sochilt","family":"Brown","sequence":"additional","affiliation":[{"name":"7Department of Hematology and Oncology, Mayo Clinic, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7482-178X","authenticated-orcid":false,"given":"James R.","family":"Cerhan","sequence":"additional","affiliation":[{"name":"8Division of Epidemiology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1962-9322","authenticated-orcid":false,"given":"Celine M.","family":"Vachon","sequence":"additional","affiliation":[{"name":"8Division of Epidemiology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5951-5055","authenticated-orcid":false,"given":"Neil E.","family":"Kay","sequence":"additional","affiliation":[{"name":"6Division of Hematology, Mayo Clinic, Rochester, MN"},{"name":"9Department of Immunology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis A.","family":"Hanson","sequence":"additional","affiliation":[{"name":"10Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Parker","sequence":"additional","affiliation":[{"name":"11College of Medicine, University of Florida, Jacksonville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3860-4830","authenticated-orcid":false,"given":"Esteban","family":"Braggio","sequence":"additional","affiliation":[{"name":"7Department of Hematology and Oncology, Mayo Clinic, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5173-4712","authenticated-orcid":false,"given":"Susan L.","family":"Slager","sequence":"additional","affiliation":[{"name":"4Division of Computational Biology, Mayo Clinic, Rochester, MN"},{"name":"6Division of Hematology, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8000-9694","authenticated-orcid":false,"given":"Christopher C.","family":"Oakes","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH"},{"name":"2The Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"7","key":"2024042515212072900_bib1","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":"15","key":"2024042515212072900_bib2","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1182\/blood.2020006322","article-title":"Natural history of monoclonal B-cell lymphocytosis among relatives in CLL families","volume":"137","author":"Slager","year":"2021","journal-title":"Blood"},{"issue":"3","key":"2024042515212072900_bib3","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1111\/bjh.17857","article-title":"Chronic lymphocytic leukaemia clones are detectable decades before diagnosis","volume":"196","author":"Vojdeman","year":"2022","journal-title":"Br J Haematol"},{"issue":"25","key":"2024042515212072900_bib4","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1182\/blood-2017-09-806398","article-title":"iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL","volume":"131","author":"Hallek","year":"2018","journal-title":"Blood"},{"issue":"7","key":"2024042515212072900_bib5","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1200\/JCO.2012.43.4449","article-title":"Overall and cancer-specific survival of patients with breast, colon, kidney, and lung cancers with and without chronic lymphocytic leukemia: a SEER population-based study","volume":"31","author":"Solomon","year":"2013","journal-title":"J\u00a0Clin Oncol"},{"issue":"15","key":"2024042515212072900_bib6","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":"1","key":"2024042515212072900_bib7","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/leu.2012.187","article-title":"Infectious complications among individuals with clinical monoclonal B-cell lymphocytosis (MBL): a cohort study of newly diagnosed cases compared to controls","volume":"27","author":"Moreira","year":"2013","journal-title":"Leukemia"},{"issue":"1","key":"2024042515212072900_bib8","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41375-020-0799-8","article-title":"Risk of serious infection among individuals with and without low count monoclonal B-cell lymphocytosis (MBL)","volume":"35","author":"Shanafelt","year":"2021","journal-title":"Leukemia"},{"issue":"7","key":"2024042515212072900_bib9","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.3324\/haematol.2017.183954","article-title":"Low-count monoclonal B-cell lymphocytosis persists after seven years of follow up and is associated with a poorer outcome","volume":"103","author":"Criado","year":"2018","journal-title":"Haematologica"},{"issue":"6","key":"2024042515212072900_bib10","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1056\/NEJMoa075290","article-title":"Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia","volume":"359","author":"Rawstron","year":"2008","journal-title":"N\u00a0Engl J Med"},{"issue":"24","key":"2024042515212072900_bib11","doi-asserted-by":"crossref","first-page":"3959","DOI":"10.1200\/JCO.2008.21.2704","article-title":"Brief report: natural history of individuals with clinically recognized monoclonal B-cell lymphocytosis compared with patients with Rai 0 chronic lymphocytic leukemia","volume":"27","author":"Shanafelt","year":"2009","journal-title":"J\u00a0Clin Oncol"},{"issue":"6","key":"2024042515212072900_bib12","doi-asserted-by":"crossref","first-page":"e237","DOI":"10.3324\/haematol.2017.183194","article-title":"Outcomes of a large cohort of individuals with clinically ascertained high-count monoclonal B-cell lymphocytosis","volume":"103","author":"Parikh","year":"2018","journal-title":"Haematologica"},{"issue":"2","key":"2024042515212072900_bib13","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1182\/blood.2020009813","article-title":"The CLL International Prognostic Index predicts outcomes in monoclonal B-cell lymphocytosis and Rai 0 CLL","volume":"138","author":"Parikh","year":"2021","journal-title":"Blood"},{"issue":"11","key":"2024042515212072900_bib14","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/ng.2443","article-title":"Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia","volume":"44","author":"Kulis","year":"2012","journal-title":"Nat Genet"},{"issue":"3","key":"2024042515212072900_bib15","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/ng.3488","article-title":"DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia","volume":"48","author":"Oakes","year":"2016","journal-title":"Nat Genet"},{"issue":"3","key":"2024042515212072900_bib16","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/leu.2014.252","article-title":"A\u00a0B-cell epigenetic signature defines three biologic subgroups of chronic lymphocytic leukemia with clinical impact","volume":"29","author":"Queiros","year":"2015","journal-title":"Leukemia"},{"issue":"8","key":"2024042515212072900_bib17","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1182\/blood.2019000490","article-title":"Developmental subtypes assessed by DNA methylation-iPLEX forecast the natural history of chronic lymphocytic leukemia","volume":"134","author":"Giacopelli","year":"2019","journal-title":"Blood"},{"issue":"5","key":"2024042515212072900_bib18","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1182\/blood-2014-09-600874","article-title":"Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations","volume":"125","author":"Baliakas","year":"2015","journal-title":"Blood"},{"issue":"10","key":"2024042515212072900_bib19","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":"20","key":"2024042515212072900_bib20","doi-asserted-by":"crossref","first-page":"5048","DOI":"10.1158\/1078-0432.CCR-18-0133","article-title":"The light chain IgLV3-21 defines a new poor prognostic subgroup in chronic lymphocytic leukemia: results of a multicenter study","volume":"24","author":"Stamatopoulos","year":"2018","journal-title":"Clin Cancer Res"},{"issue":"8","key":"2024042515212072900_bib21","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.1073\/pnas.1913810117","article-title":"IGLV3-21\u221701 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling","volume":"117","author":"Maity","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"21","key":"2024042515212072900_bib22","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1182\/blood.2020008311","article-title":"IGLV3-21R110 identifies an aggressive biological subtype of chronic lymphocytic leukemia with intermediate epigenetics","volume":"137","author":"Nadeu","year":"2021","journal-title":"Blood"},{"issue":"13","key":"2024042515212072900_bib23","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.3390\/cancers14133045","article-title":"Immunoglobulin gene sequence as an inherited and acquired risk factor for chronic lymphocytic leukemia","volume":"14","author":"Datta","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"1","key":"2024042515212072900_bib24","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1365-2141.2011.09010.x","article-title":"Monoclonal B-cell lymphocytosis is closely related to chronic lymphocytic leukaemia and may be better classified as early-stage CLL","volume":"157","author":"Kern","year":"2012","journal-title":"Br J Haematol"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/143\/17\/1752\/2223027\/blood_bld-2023-022180-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/143\/17\/1752\/2223027\/blood_bld-2023-022180-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T15:21:43Z","timestamp":1714058503000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/143\/17\/1752\/507073\/Prediction-of-outcomes-for-high-count-monoclonal-B"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,25]]},"references-count":24,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2024,4,25]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2023022180","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,25]]}}}