{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:35:35Z","timestamp":1790804135520,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"crossref","award":["9980"],"award-info":[{"award-number":["9980"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"crossref","award":["1426"],"award-info":[{"award-number":["1426"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"crossref","award":["15426"],"award-info":[{"award-number":["15426"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Associazione Italiana contro le Leucemie-Linfomi e Mieloma"},{"name":"Gilead fellowship program"},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["RF-2021-12374376"],"award-info":[{"award-number":["RF-2021-12374376"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Policlinico San Martino","award":["5M-2023-23687130"],"award-info":[{"award-number":["5M-2023-23687130"]}]},{"name":"Guido Berlucchi Foundation"},{"name":"Umberto Veronesi Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Background\/Objectives: The immunoglobulin heavy-chain variable (IGHV) gene repertoire represents a characteristic feature of chronic lymphocytic leukemia (CLL), although its configuration is not well defined at the early disease stages. The IGHV repertoire of a cohort of early CLL patients was analyzed and compared to that of a \u201creal-world\u201d reference cohort. Methods: Patients from the O-CLL1 observational protocol, which enrolled only Binet stage A cases within twelve months from diagnosis, were studied. IGHV\/IGHJ rearrangements were sequenced and annotated following ERIC recommendations, and stereotyped subsets were assigned using ARResT\/AssignSubsets. The repertoire features were compared with the dataset of a real-world cohort of patients with heterogeneous staging (CTR cohort) and with published early-diagnosis series. Results: IGHV and IGHJ gene distributions and HCDR3-length profiles in O-CLL1 closely mirrored those of CTR, indicating that the BcR IG repertoire at diagnosis is already defined rather than being selected during disease progression. Mutated IGHV (M-CLL) predominated, with a frequency of stereotyped BcR IG comparable to that of other early-diagnosis cohorts. However, within this conserved framework, subset #4 was over-represented among M-CLL from O-CLL without an increased overall IGHV4-34 gene usage, suggestive of a selective expansion rather than a recombinational bias. Subset #4 cases retained canonical HCDR3 motifs and showed time-to-first-treatment like other M-CLL, likely reflecting the younger age structure of O-CLL1. Conclusions: Early-diagnosis CLL displays a biased IGHV repertoire with stereotyped configurations characteristic of CLL, including subsets that are rare in the normal B-cell repertoire. These findings support a central role for antigen-driven selection in shaping CLL evolution.<\/jats:p>","DOI":"10.3390\/antib15020025","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:11:12Z","timestamp":1773828672000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunogenetic Architecture of Chronic Lymphocytic Leukemia at Early Stage: Insights from the O-CLL1 Cohort"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7889-8103","authenticated-orcid":false,"given":"Davide","family":"Bagnara","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Nicola","family":"Mazzarello","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy"},{"name":"Molecular Pathology Unit, IRCCS Azienda Ospedaliera Metroplitana, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5512-8106","authenticated-orcid":false,"given":"Monica","family":"Colombo","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, IRCCS Azienda Ospedaliera Metroplitana, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1479-8121","authenticated-orcid":false,"given":"Ennio","family":"Nano","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, IRCCS Azienda Ospedaliera Metroplitana, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4021-1631","authenticated-orcid":false,"given":"Niccol\u00f2","family":"Cardente","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Oslo, 0424 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5097-6640","authenticated-orcid":false,"given":"Fabiana","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy"},{"name":"Molecular Pathology Unit, IRCCS Azienda Ospedaliera Metroplitana, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4591-3260","authenticated-orcid":false,"given":"Nadia","family":"Bertola","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, IRCCS Azienda Ospedaliera Metroplitana, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7302-7429","authenticated-orcid":false,"given":"Vanessa","family":"Cossu","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy"},{"name":"Molecular Pathology Unit, IRCCS Azienda Ospedaliera Metroplitana, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2301-8698","authenticated-orcid":false,"given":"Fabio","family":"Ghiotto","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalberto","family":"Ibatici","sequence":"additional","affiliation":[{"name":"Hematology and Cellular Therapy Unit, Azienda Ospedaliera Metroplitana, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6512-6080","authenticated-orcid":false,"given":"Emanuele","family":"Angelucci","sequence":"additional","affiliation":[{"name":"Hematology and Cellular Therapy Unit, Azienda Ospedaliera Metroplitana, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Neri","sequence":"additional","affiliation":[{"name":"Scientific Directorate, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Gentile","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Onco-Hematology, AO of Cosenza, 87100 Cosenza, Italy"},{"name":"Department of Pharmacy, Health and Nutritional Science, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2585-7073","authenticated-orcid":false,"given":"Fortunato","family":"Morabito","sequence":"additional","affiliation":[{"name":"Gruppo Amici Dell\u2019Ematologia Foundation-GrADE, 42100 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manlio","family":"Ferrarini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3335-1101","authenticated-orcid":false,"given":"Giovanna","family":"Cutrona","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, IRCCS Azienda Ospedaliera Metroplitana, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6643-7083","authenticated-orcid":false,"given":"Franco","family":"Fais","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy"},{"name":"Molecular Pathology Unit, IRCCS Azienda Ospedaliera Metroplitana, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bagnara, D., Mazzarello, A.N., Ghiotto, F., Colombo, M., Cutrona, G., Fais, F., and Ferrarini, M. 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HO"}],"container-title":["Antibodies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4468\/15\/2\/25\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T05:20:07Z","timestamp":1773984007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4468\/15\/2\/25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":36,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["antib15020025"],"URL":"https:\/\/doi.org\/10.3390\/antib15020025","relation":{},"ISSN":["2073-4468"],"issn-type":[{"value":"2073-4468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]}}}