{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:40:38Z","timestamp":1759970438134,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Early Cancer Research Initiative Network on MBL (ECRINM3)","award":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"],"award-info":[{"award-number":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"]}]},{"DOI":"10.13039\/501100014139","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"],"award-info":[{"award-number":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"],"award-info":[{"award-number":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FONDOS FEDER","award":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"],"award-info":[{"award-number":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"]}]},{"name":"Fondo Europeo de Desarrollo Regional","award":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"],"award-info":[{"award-number":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"]}]},{"DOI":"10.13039\/501100004837","name":"Juan de la Cierva -Incorporaci\u00f3n-","doi-asserted-by":"publisher","award":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"],"award-info":[{"award-number":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie","award":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"],"award-info":[{"award-number":["CB16\/12\/00400","PI22\/00674","0639-IDIAL-NET-3-3","IJC2020-044160-I","101034371"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Despite the current international prognostic index for chronic lymphocytic leukemia (CLL) being widely accepted and broadly used, it does not consider the kinetics of the B-cell clone over time. Here, we investigated the potential association between distinct features of leukemic cells and other immune cells in blood and the kinetics of clonal B-cells in CLL stage Binet A\/Rai 0 (A\/0) patients; Methods: Based on the leukemia cell kinetics, 69 CLL A\/0 cases followed for a median of 105 months were classified as carrying stable (n = 53) vs. rapidly increasing in size (n = 16) CLL clones; Results: Patients with increasing CLL clones had a significantly higher risk of disease progression and shortened time to first therapy vs. those carrying stable B-cell clones (p \u2264 0.001). Strikingly, the distribution of various immune-cell populations in blood at diagnosis also differed significantly between the two groups, with lower T\u03b1\u03b2 CD4+CD8lo cell counts (p = 0.03), a greater switched\/unswitched memory B-cell ratio (p = 0.01), and higher plasma cell counts (p = 0.05) in CLL with increasing vs. stable clones. Multivariate analysis revealed that the number of circulating clonal B-cells (\u226515 \u00d7 109\/L) and T\u03b1\u03b2 CD4+CD8lo cells (\u226435 cells\/\u00b5L), together with an IGHV unmutated gene status at diagnosis, were independent predictors of an increasing CLL clone; Conclusions: Altogether, these data suggest that the expansion of the CLL clone in stage A\/0 patients may depend on both the intrinsic characteristics of CLL cells and the surrounding immune microenvironment.<\/jats:p>","DOI":"10.3390\/cancers17030347","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T11:47:32Z","timestamp":1737460052000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Normal Residual Lymphoid Cell Populations in Blood as Surrogate Biomarker of the Leukemia Cell Kinetics in CLL BinetA\/Rai 0"],"prefix":"10.3390","volume":"17","author":[{"given":"Fernando","family":"Solano","sequence":"first","affiliation":[{"name":"Hematology Service, Hospital General Universitario Nuestra Se\u00f1ora del Prado, 45600 Talavera de la Reina, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Criado","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC\u2014University of Salamanca), 37007 Salamanca, Spain"},{"name":"Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca (Universidad de Salamanca), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahir","family":"Moreno","sequence":"additional","affiliation":[{"name":"Hematology Service, Hospital General Universitario Nuestra Se\u00f1ora del Prado, 45600 Talavera de la Reina, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Gomez-Gonzalez","sequence":"additional","affiliation":[{"name":"Hematology Service, Hospital General Universitario Nuestra Se\u00f1ora del Prado, 45600 Talavera de la Reina, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Lerma-Verdejo","sequence":"additional","affiliation":[{"name":"Hematology Service, Hospital General Universitario Nuestra Se\u00f1ora del Prado, 45600 Talavera de la Reina, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2097-7199","authenticated-orcid":false,"given":"Cristina","family":"Teodosio","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC\u2014University of Salamanca), 37007 Salamanca, Spain"},{"name":"Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca (Universidad de Salamanca), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Dolores","family":"Martinez-Moya","sequence":"additional","affiliation":[{"name":"Hematology Service, Hospital General Universitario Nuestra Se\u00f1ora del Prado, 45600 Talavera de la Reina, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iryna","family":"Luts","sequence":"additional","affiliation":[{"name":"Hematology Service, Hospital General Universitario Nuestra Se\u00f1ora del Prado, 45600 Talavera de la Reina, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Contreras","sequence":"additional","affiliation":[{"name":"Biochemistry Service, University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9653-9849","authenticated-orcid":false,"given":"Guillermo","family":"Oliva-Ariza","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC\u2014University of Salamanca), 37007 Salamanca, Spain"},{"name":"Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca (Universidad de Salamanca), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blanca","family":"Fuentes Herrero","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC\u2014University of Salamanca), 37007 Salamanca, Spain"},{"name":"Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca (Universidad de Salamanca), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Manuel","family":"Serrano-Lozano","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC\u2014University of Salamanca), 37007 Salamanca, Spain"},{"name":"Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca (Universidad de Salamanca), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-8917","authenticated-orcid":false,"given":"Julia","family":"Almeida","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC\u2014University of Salamanca), 37007 Salamanca, Spain"},{"name":"Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca (Universidad de Salamanca), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7230","authenticated-orcid":false,"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC\u2014University of Salamanca), 37007 Salamanca, Spain"},{"name":"Cytometry Service, NUCLEUS, Department of Medicine, University of Salamanca (Universidad de Salamanca), 37007 Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1002\/ajh.26367","article-title":"Chronic Lymphocytic Leukemia: 2022 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