Immune Profiling Along with Vitamin D and Their Association with Genetic Risk Stratification in Newly Diagnosed Acute Myeloid Leukemia: Poor Risk Group Correlates with Activated T Regulatory Cells.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy traditionally risk-stratified by genetic abnormalities. However, immune dysregulation is increasingly recognized as a key factor in AML pathophysiology and prognosis. Our study examined the levels of cellular and metabolic immune markers, including Programmed cell death ligand 1 (PDL1) in blasts, T-cell subsets in peripheral blood, and serum metabolic regulators (kynurenine and vitamin D), to investigate their immunomodulatory roles and associations with disease characteristics in AML. We analysed 71 newly diagnosed AML patients (median age, 32 years; range, 14-62), stratified by the European Leukemia Net (ELN) 2017 criteria into good (27%), intermediate (56%), and poor (17%) risk groups. Immune profiling included flow cytometric analysis of PD-L1 on blasts and T cell subsets in peripheral blood, performed by sequential gating. Serum vitamin D and kynurenine levels were assessed using standard biochemical assays. Poor-risk AML patients showed a significantly higher proportion of activated T-regulatory cells (28.3%) compared to good (8.7%) and intermediate (5.1%) risk groups (p = 0.046). There was a non-significant trend toward higher PD-L1 expression in poor-risk group (7.1%) compared to good (2%) and intermediate (1.75%) risk groups (p = 0.35). Median vitamin D levels were lower in the poor-risk group (14.4 ng/ml) compared to good (17.1 ng/ml) and intermediate (16.6 ng/ml). Cytotoxic T-cells and other T-cell subsets did not show any difference among the different risk groups. Our findings suggest a link between adverse genetic risk group and adverse immunosuppressive phenotype that can pave the way for potential therapeutic interventions directed at the altered immune microenvironment. The online version contains supplementary material available at https://doi.org/10.1007/s12288-025-02217-2.