Integrin Α4 (ITGA4) Overexpression Is Associated with Advanced Clinical Features and Diagnostic Potential in Chronic Lymphocytic Leukemia

Background: Chronic lymphocytic leukemia (CLL) remains clinically heterogeneous, necessitating reliable biomarkers for early diagnosis and risk stratification. Integrin α4 (ITGA4), which mediates cell adhesion and homing, is implicated in CLL pathogenesis, but its precise clinical and diagnostic utility based on gene regulation status has not been comprehensively evaluated. Patients and Methods: This case-control study compared newly diagnosed CLL patients to a control group. The study enrolled 74 participants, including CLL patients and controls, categorized into down-regulation (n=17), normal-regulation (n=25), and up-regulation (n=32) groups based on ITGA4 gene expression levels. Clinical, demographic, hematological, and immunological data were collected. Statistical analysis utilized Chi-square or Exact tests for categorical data, one-way ANOVA or Kruskal-Wallis tests for numerical data, and logistic regression to identify independent predictors of CLL diagnosis. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic efficacy of ITGA4 regulation, compared to β2-microglobulin. Results: ITGA4 up-regulation was significantly associated with several adverse clinical features, including CLL diagnosis (84.4% in the up-regulated group; p < 0.001), splenomegaly, lymphadenopathy, and bone marrow hypercellularity (p < 0.001). ITGA4 regulation emerged as a highly significant independent predictor of CLL (OR: 2.95; p < 0.001). Furthermore, ITGA4 demonstrated excellent diagnostic performance for CLL, with AUC of 0.856 (p < 0.0001). Conclusion: Elevated ITGA4 gene regulation is strongly linked to the clinical phenotype of CLL involving significant organ infiltration and is a robust, independent diagnostic biomarker with performance exceeding that of β2-microglobulin. These findings support the utility of ITGA4 expression analysis for the accurate diagnosis and potential risk stratification of CLL patients.