Adverse Effects of Low Serum <scp>HDL</scp> ‐C Levels on Prognosis and Tumor Immune Microenvironment in Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

Disorders of lipid metabolism contribute to the occurrence and progression of hematological malignancies, including chronic lymp hocytic leukemia (CLL). 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-CLL). Our survival analysis showed that low levels of high-density lipoprotein cholesterol/Apolipoprotein-A1 (HDL-C/ApoA1) were associated with poor overall survival (OS) and progression-free survival in patients with ND-CLL. Multivariate analysis identified HDL-C as an independent hazard element for OS. A nomogram combining HDL-C levels and classical prognostic factors increased the accuracy of predicting 5-year OS compared to prediction based solely on classical prognostic factors. The adverse effect of low levels of HDL-C on prognosis in CLL patients was further validated through external validation, wherein the functionality of HDL-C 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-C/ApoA1 was significantly positively correlated with natnatural killer (NK) cells. Subsequent in vitro cell experiments confirmed the ability of HDL to augment NK cell cytotoxicity, as evidenced by elevated expression levels of CD107a and tumor necrosis factor-α. In conclusion, low serum HDL-C levels are related to a poor prognosis in patients with ND-CLL, potentially due to impaired NK cell cytotoxicity, providing insight into the prognostic role of HDL-C and proposing a new potential therapeutic target in patients with ND-CLL.