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The objective of this study was to investigate the association between serum lipid levels and prognosis in patients with CLL. We retrospectively analyzed data from 142 patients with newly diagnosed CLL (ND\u2010CLL). Our survival analysis showed that low levels of high\u2010density lipoprotein cholesterol\/Apolipoprotein\u2010A1 (HDL\u2010C\/ApoA1) were associated with poor overall survival (OS) and progression\u2010free survival in patients with ND\u2010CLL. Multivariate analysis identified HDL\u2010C as an independent hazard element for OS. A nomogram combining HDL\u2010C levels and classical prognostic factors increased the accuracy of predicting 5\u2010year OS compared to prediction based solely on classical prognostic factors. The adverse effect of low levels of HDL\u2010C on prognosis in CLL patients was further validated through external validation, wherein the functionality of HDL\u2010C was simulated by assessing cholesterol efflux in a cohort comprising 448 CLL patients. Moreover, flow cytometry analysis of 194 peripheral blood lymphocyte subpopulations demonstrated that the levels of HDL\u2010C\/ApoA1 was significantly positively correlated with natnatural killer (NK) cells. Subsequent in\u00a0vitro cell experiments confirmed the ability of HDL to augment NK cell cytotoxicity, as evidenced by elevated expression levels of CD107a and tumor necrosis factor\u2010\u03b1. In conclusion, low serum HDL\u2010C levels are related to a poor prognosis in patients with ND\u2010CLL, potentially due to impaired NK cell cytotoxicity, providing insight into the prognostic role of HDL\u2010C and proposing a new potential therapeutic target in patients with ND\u2010CLL.<\/jats:p>","DOI":"10.1002\/cam4.71791","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T03:05:11Z","timestamp":1776222311000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adverse Effects of Low Serum\n                    <scp>HDL<\/scp>\n                    \u2010C Levels on Prognosis and Tumor Immune Microenvironment in Patients With Newly Diagnosed Chronic Lymphocytic Leukemia"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8857-6686","authenticated-orcid":false,"given":"Weiran","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010Sen University Cancer Center  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shutong","family":"Liu","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangtao","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010Sen University Cancer Center  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010Sen University Cancer Center  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaze","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010Sen University Cancer Center  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010Sen University Cancer Center  Guangzhou P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010Sen University Cancer Center  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4226-9580","authenticated-orcid":false,"given":"Yang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010Sen University Cancer Center  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"e_1_2_11_2_1","article-title":"Chronic Lymphocytic Leukaemia","volume":"3","author":"Kipps T. 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