{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:15:32Z","timestamp":1792883732586,"version":"4.5.0"},"reference-count":80,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Therapy for chronic lymphocytic leukemia (CLL) has evolved dramatically with the introduction of targeted agents, particularly Bruton tyrosine kinase inhibitors (BTKis) and BCL2 inhibitors (BCL2is). This review summarizes contemporary frontline and relapsed\/refractory treatment strategies, with an emphasis on molecular risk stratification, combination and triplet regimens, measurable residual disease (MRD)\u2013guided therapy, and time-limited approaches. We further examine how genomic complexity, prior therapies, and sociodemographic factors influence disease progression, treatment resistance, and clinical outcomes.<\/jats:p>","DOI":"10.3390\/ijms27115117","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:43:04Z","timestamp":1780648984000},"page":"5117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chronic Lymphocytic Leukemia: Molecular Pathologies and Therapeutic Strategies"],"prefix":"10.3390","volume":"27","author":[{"given":"Kelly","family":"Meza","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Barrientos Risso","sequence":"additional","affiliation":[{"name":"Baystate Medical Center, University of Massachusetts Chan Medical School, Springfield, MA 01107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"},{"name":"Rutgers Cancer Institute, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8176-2342","authenticated-orcid":false,"given":"Carla","family":"Romagnoli","sequence":"additional","affiliation":[{"name":"Mount Sinai Medical Center, Miami Beach, FL 33140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Sandoval","sequence":"additional","affiliation":[{"name":"Moffitt Malignant Hematology & Cellular Therapy at Memorial Healthcare System, Pembroke Pines, FL 33028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelida","family":"Brauchle","sequence":"additional","affiliation":[{"name":"Mount Sinai Medical Center, Miami Beach, FL 33140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Lyubimova","sequence":"additional","affiliation":[{"name":"Mount Sinai Medical Center, Miami Beach, FL 33140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leily","family":"Santos","sequence":"additional","affiliation":[{"name":"Mount Sinai Medical Center, Miami Beach, FL 33140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Goya Balaguer","sequence":"additional","affiliation":[{"name":"Mount Sinai Medical Center, Miami Beach, FL 33140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6018-5535","authenticated-orcid":false,"given":"Jacqueline","family":"Barrientos","sequence":"additional","affiliation":[{"name":"Mount Sinai Medical Center, Miami Beach, FL 33140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1182\/blood-2018-09-873083","article-title":"Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact","volume":"133","author":"Baliakas","year":"2019","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/S1470-2045(24)00070-6","article-title":"First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA\/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial","volume":"25","author":"Kater","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1182\/blood.2020009530","article-title":"Low-burden TP53 mutations in CLL: Clinical impact 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