CD69 predicts prognosis through immune cell infiltration and decitabine treatment response in acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous myeloid neoplasm. Recent studies have focused on unraveling the complexities of the tumor microenvironment (TME) and its impact on AML, with a specific emphasis on CD69, a potential TME regulator. However, the precise relationship between CD69 and AML is yet to be fully elucidated. This study aimed to analyze the heterogeneous gene expression landscape of AML patients using public databases, and to elucidate the relationship between CD69 expression and the pathophysiology of AML. METHODS: Three gene datasets from Gene Expression Omnibus (GEO), ribonucleic acid (RNA) sequence data from The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and tumor cell lines data from Cancer Cell Line Encyclopedia (CCLE) were used. The Cox proportional hazards regression model was employed to assess the impact of differentially expressed genes on the overall survival (OS) rate of AML. Spearman's rank correlation coefficient analysis was conducted to determine the relationship between CD69 and immune cell infiltration in AML patients. Western blot analysis was utilized to verify CD69 expression in AML cell lines. RESULTS: (I) Gene expression: 13 differentially expressed genes were identified in AML. (II) Impact on survival: CD69 expression was inversely related to OS of AML patients, with lower CD69 levels correlating with improved survival outcomes. (III) Independent risk factors: CD69, ITGB7, SCD and age were identified as independent risk factors in AML. (IV) Immune cell infiltration: a higher expression of CD69 was associated with reduced infiltration of CD8+ T cells and macrophages in AML. (V) Effect of decitabine (DA) treatment: AML patients treated with DA exhibited decreased CD69 expression. CONCLUSIONS: The study established a correlation between the expression of ITGB7, SCD, CD69 and the OS in AML patients. SCD, ITGB7 and age were identified as key prognostic factors. The multifaceted role of CD69 in AML, encompassing its association with prognosis, immune cell infiltration, and response to chemotherapy, underscores its potential as a key player in the complex landscape of AML pathogenesis and treatment response.