{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:42:59Z","timestamp":1792795379977,"version":"4.5.0"},"reference-count":122,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Chronic Lymphocytic Leukemia (CLL) is the most frequent type of leukemia in Western countries. In recent years, there have been important advances in the knowledge of molecular alterations that underlie the disease\u2019s pathogenesis. Very heterogeneous prognostic subgroups have been identified by the mutational status of immunoglobulin heavy variable genes (IGVH), FISH analysis and molecular evaluation of TP53 mutations. Next-generation sequencing (NGS) technologies have provided a deeper characterization of the genomic and epigenomic landscape of CLL. New therapeutic targets have led to a progressive reduction of traditional chemoimmunotherapy in favor of specific biological agents. Furthermore, in the latest clinical trials, the minimal residual disease (MRD) has emerged as a potent marker of outcome and a guide to treatment duration. This review focuses on recent insights into the understanding of CLL biology. We also consider the translation of these findings into the development of risk-adapted and targeted therapeutic approaches.<\/jats:p>","DOI":"10.3390\/cancers16203483","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T12:44:31Z","timestamp":1728909871000},"page":"3483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Recent Advances in the Molecular Biology of Chronic Lymphocytic Leukemia: How to Define Prognosis and Guide Treatment"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5337-5947","authenticated-orcid":false,"given":"Annalisa","family":"Arcari","sequence":"first","affiliation":[{"name":"Hematology Unit, Ospedale Guglielmo da Saliceto, Azienda USL di Piacenza, 29100 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Morello","sequence":"additional","affiliation":[{"name":"Hematology Unit, Ospedale Guglielmo da Saliceto, Azienda USL di Piacenza, 29100 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1184-8709","authenticated-orcid":false,"given":"Elena","family":"Borotti","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplant Laboratory, Molecular Diagnostic and Stem Cells Manipulation, Ospedale Guglielmo da Saliceto, Azienda USL di Piacenza, 29100 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5920-7386","authenticated-orcid":false,"given":"Elena","family":"Ronda","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplant Laboratory, Molecular Diagnostic and Stem Cells Manipulation, Ospedale Guglielmo da Saliceto, Azienda USL di Piacenza, 29100 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Rossi","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplant Laboratory, Molecular Diagnostic and Stem Cells Manipulation, Ospedale Guglielmo da Saliceto, Azienda USL di Piacenza, 29100 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Vallisa","sequence":"additional","affiliation":[{"name":"Hematology Unit, Ospedale Guglielmo da Saliceto, Azienda USL di Piacenza, 29100 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1001\/jama.2023.1946","article-title":"Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Review","volume":"329","author":"Shadman","year":"2023","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41408-021-00556-7","article-title":"Survival of patients with chronic lymphocytic leukemia before and after the introduction of chemoimmunotherapy in Germany","volume":"11","author":"Wellmann","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/bjh.16397","article-title":"Survival continues to increase in chronic lymphocytic leukaemia: A population-based analysis among 20 468 patients diagnosed in the Netherlands between 1989 and 2016","volume":"189","author":"Levin","year":"2020","journal-title":"Br. 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