{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:50:56Z","timestamp":1790974256167,"version":"4.1.0"},"reference-count":342,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Clinical Medicine, Aarhus University"},{"name":"Karen Elise Jensen Foundation"},{"name":"Merchant Einar Willumsen\u2019s Memorial Foundation"},{"name":"Danish Lymphoma Group"},{"name":"Peter and Alice Madsen"},{"name":"Knud and Edith Eriksen\u2019s Memorial Foundation"},{"name":"Eva and Henry Fr\u00e6nkel\u2019s Memorial Foundation"},{"name":"Raimond and Dagmar Ringg\u00e5rd-Bohn\u2019s Foundatio"},{"name":"Butcher Max W\u00f8rzner and wife W\u00f8rzner\u2019s Memorial Grant"},{"name":"Master Carpenter J\u00f8rgen Holm and wife Elisa F. Hansen\u2019s Memorial Grant"},{"name":"A. P. M\u00f8ller Foundation for the Advancement of Medical Sciences"},{"name":"Dagmar Marshall\u2019s Foundation"},{"name":"Farmer of \u201c\u00d8lufg\u00e5rd\u201d Peder Nielsen Kristensen\u2019s Memorial Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Follicular lymphoma (FL) is the most prevalent indolent B-cell lymphoma entity, often characterized by the t(14;18) BCL2-IGH translocation. The malignancy represents a clinically and biologically highly heterogeneous disease. Most patients have favorable prognoses; however, despite therapeutic advancements, the disease remains incurable, with recurrent relapses or early disease progression. Moreover, transformation to an aggressive histology, most often diffuse large-B-cell lymphoma, remains a critical event in the disease course, which is associated with poor outcomes. Understanding the individual patient\u2019s risk of transformation remains challenging, which has motivated much research on novel biomarkers within the past four decades. This review systematically assessed the research on molecular biomarkers in FL transformation and outcome. Following the PRISMA guidelines for systemic reviews, the PubMed database was searched for English articles published from January 1984 through September 2024, yielding 6769 results. The identified publications were carefully screened and reviewed, of which 283 original papers met the inclusion criteria. The included studies focused on investigating molecular biomarkers as predictors of transformation or as prognostic markers of time-related endpoints (survival, progression, etc.). The effects of each biomarker were categorized based on their impact on prognosis or risk of transformation as none, favorable, or inferior. The biomarkers included genetic abnormalities, gene expression, microRNAs, markers of B cells\/FL tumor cells, markers of the tumor microenvironment, and soluble biomarkers. This comprehensive review provides an overview of the research conducted in the past four decades, underscoring the persistent challenge in risk anticipation of FL patients.<\/jats:p>","DOI":"10.3390\/ijms252011179","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T11:19:18Z","timestamp":1729163958000},"page":"11179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4086-5183","authenticated-orcid":false,"given":"Marie Hairing","family":"Enemark","sequence":"first","affiliation":[{"name":"Department of Hematology, Aarhus University Hospital, 8200 Aarhus N, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5706-3407","authenticated-orcid":false,"given":"Jonas Klejs","family":"Hemmingsen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Aarhus University Hospital, 8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja Lund","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Aarhus University Hospital, 8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0287-7124","authenticated-orcid":false,"given":"Robert","family":"Kridel","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5089-3271","authenticated-orcid":false,"given":"Maja","family":"Ludvigsen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Aarhus University Hospital, 8200 Aarhus N, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 revision of the World Health Organization classification of lymphoid neoplasms","volume":"127","author":"Swerdlow","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/hon.3138","article-title":"Update on follicular lymphoma","volume":"41","author":"Friedberg","year":"2023","journal-title":"Hematol. 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