{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:09:08Z","timestamp":1773335348498,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["DS 653"],"award-info":[{"award-number":["DS 653"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["DS 640"],"award-info":[{"award-number":["DS 640"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is characterized by dysregulated apoptosis and metabolic reprogramming, including alterations in lipid metabolism. However, the plasma lipidome of newly diagnosed, treatment-na\u00efve CLL patients remains insufficiently characterized. This study aimed to define disease-specific plasma lipidomic alterations, identify discriminatory lipid species, and investigate associated metabolic pathways. Methods: The study cohort consisted of 41 participants (median age 75 years, range: 40\u201386), including 30 newly diagnosed, treatment-na\u00efve CLL patients (median age 75 years, range: 40\u201386) and 11 age- and sex-matched healthy controls (median age 75 years, range: 41\u201385). Targeted lipidomic profiling was performed on plasma samples using liquid chromatography with tandem mass spectrometry (LC-MS\/MS). Data processing was conducted in R using LipidSigR. Statistical analyses employed the Wilcoxon\u2013Mann\u2013Whitney test with Benjamini\u2013Hochberg correction. To address data dimensionality, Boruta machine learning and pathway enrichment analyses were applied. Gene\u2013lipid associations were further explored using GATOm, followed by Metascape analysis to identify enriched biological processes. Results: A total of 124 lipid species from five major classes (phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, ether-linked phosphatidylcholines, and acylcarnitines) were quantified. CLL patients exhibited significant enrichment of acylcarnitines, saturated phosphatidylcholines, and sphingolipids compared with controls. Principal component analysis showed partial separation by disease status. Machine learning identified carnitines and ether-linked phospholipids as key discriminators. Integrated gene\u2013lipid analyses revealed significant enrichment of lipid metabolism-related pathways, particularly glycerolipid and phosphatidylcholine metabolism, as well as lipid catabolism, ether lipid metabolism, and fatty acid metabolism. Conclusions: Treatment-na\u00efve CLL patients display distinct plasma lipidomic signatures indicative of disease-specific metabolic reprogramming. Integrated lipidomic and predictive pathway analyses suggest disruptions in lipid metabolic pathways and highlight carnitines and ether-linked phospholipids as biological markers warranting further investigation as potential CLL biomarkers.<\/jats:p>","DOI":"10.3390\/cancers18060896","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T17:04:24Z","timestamp":1773162264000},"page":"896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Specific Lipidomic Shifts in Chronic Lymphocytic Leukemia at Diagnosis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0769-5880","authenticated-orcid":false,"given":"Julia","family":"Wojnicka","sequence":"first","affiliation":[{"name":"Department of Pathobiochemistry and Interdisciplinary Applications of Ion Chromatography, Medical University of Lublin, 1 Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-6217","authenticated-orcid":false,"given":"Micha\u0142","family":"Kie\u0142bus","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical University of Lublin, 1 Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9530-6659","authenticated-orcid":false,"given":"Paulina","family":"Mertowska","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-1396","authenticated-orcid":false,"given":"Sebastian","family":"Mertowski","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-4741","authenticated-orcid":false,"given":"Ewelina","family":"Grywalska","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Medical University of Lublin, 4a Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4261-269X","authenticated-orcid":false,"given":"Piotr","family":"Sosnowski","sequence":"additional","affiliation":[{"name":"Department of Bioanalytics, Medical University of Lublin, 8b Jaczewskiego St., 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicja","family":"Wielgosz","sequence":"additional","affiliation":[{"name":"Department of Bioanalytics, Medical University of Lublin, 8b Jaczewskiego St., 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kozub-P\u0119drak","sequence":"additional","affiliation":[{"name":"Department of Bioanalytics, Medical University of Lublin, 8b Jaczewskiego St., 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3536-8035","authenticated-orcid":false,"given":"Barbara","family":"Sosnowska-Pasiarska","sequence":"additional","affiliation":[{"name":"Department of Oncocardiology, Holy Cross Cancer Center, 25-734 Kielce, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Klatka","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetology, Medical University of Lublin, 1 G\u0119bali St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janusz","family":"Klatka","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Laryngological Oncology, Medical University of Lublin, 8 Jaczewskiego St., 20-954 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9758-5831","authenticated-orcid":false,"given":"Anna","family":"B\u0142a\u017cewicz","sequence":"additional","affiliation":[{"name":"Department of Pathobiochemistry and Interdisciplinary Applications of Ion Chromatography, Medical University of Lublin, 1 Chod\u017aki St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.clml.2025.07.012","article-title":"Survival Outcomes in Patients with Chronic Lymphocytic Leukemia: A SEER Analysis","volume":"26","author":"Modi","year":"2026","journal-title":"Clin. 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