{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T23:18:34Z","timestamp":1778887114837,"version":"3.51.4"},"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005009","name":"Stiftelsen Assar Gabrielssons Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010107","name":"Anna-Lisa och Bror Bj\u00c3\u00b6rnssons Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010107","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014552","name":"Adlerbertska Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014552","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009479","name":"Kungl. Vetenskaps- och Vitterhets-Samh\u00c3\u00a4llet i G\u00c3\u00b6teborg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["PAT3959823"],"award-info":[{"award-number":["PAT3959823"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG28768"],"award-info":[{"award-number":["IG28768"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u00c5\u201aodowska-Curie Actions","doi-asserted-by":"publisher","award":["No101034307"],"award-info":[{"award-number":["No101034307"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Chronic lymphocytic leukemia (CLL) is divided into unmutated (UM-CLL) and mutated (M-CLL) subtypes depending on somatic hypermutation (SHM) frequency in their immunoglobulin heavy chain V (IGHV) region. We previously demonstrated that CD27\n                    <jats:sup>bright<\/jats:sup>\n                    memory B cells (MBCs) are germinal center (GC)-dependent with higher mutation rate, whereas CD27\n                    <jats:sup>dull<\/jats:sup>\n                    MBCs accumulate fewer mutations and originate independently from the GC. We conducted a meta-transcriptomic analysis on bulk RNA data from 116 individuals combining four CLL cohorts and healthy B cell subsets (na\u00efve, CD27\n                    <jats:sup>dull<\/jats:sup>\n                    and CD27\n                    <jats:sup>bright<\/jats:sup>\n                    MBCs) to decipher the transcriptional and mechanistic functions of CLL subtypes. CD27\n                    <jats:sup>bright<\/jats:sup>\n                    MBCs showed more transcriptional similarity to M-CLL rather than UM-CLL. Functional enrichment analysis revealed that\n                    <jats:italic>LPL<\/jats:italic>\n                    ,\n                    <jats:italic>\n                      <jats:italic>ZNF667<\/jats:italic>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>ZNF667-AS1<\/jats:italic>\n                    are potential informative biomarkers for stratification of CLL subtypes. They are part of the mechanistic regulatory pathways of CLL pathology through cholesterol and Epithelial Mesenchymal Transition (EMT) regulation. We applied markers for the GC B-cell substages to map\n                    <jats:italic>\n                      <jats:italic>in silico<\/jats:italic>\n                    <\/jats:italic>\n                    the CLL cohorts to their potential GC B cell counterpart. UM-CLL represented transcriptional mimicry to an early intermediary GC substage whereas M-CLL mimicked later substages in the GC. This could potentially explain the IGHV mutational status of M-CLL as well as hypothesize that CLL subtypes could derive from a GC-dependent pathway.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0335069","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:43:52Z","timestamp":1761155032000},"page":"e0335069","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Germinal center trajectories and transcriptional signatures define CLL subtypes and their pathway regulators"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1121-1527","authenticated-orcid":true,"given":"Ahmed","family":"Mohamed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Giudice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Bas\u00edlio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina","family":"Barresi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeep Kumar","family":"Kopparapu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanda","family":"Friman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarja","family":"Malm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Tilevik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2064-2556","authenticated-orcid":true,"given":"Ola","family":"Grimsholm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"issue":"5","key":"pone.0335069.ref001","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1056\/NEJMra1908213","article-title":"Treatment 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