Unlocking the potential: A novel prognostic index signature for acute myeloid leukemia.

ABSTRACT

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by challenges in treatment, including drug resistance and frequent relapse. Recent research highlights the crucial roles of tumor microenvironment (TME) in assisting tumor cell immune escape and promoting tumor aggressiveness. This study delves into the interplay between AML and TME. Through the exploration of potential driver genes, we constructed an AML prognostic index (AMLPI). Cross-platform data and multi-dimensional internal and external validations confirmed that the AMLPI outperforms existing models in terms of areas under the receiver operating characteristic curves, concordance index values, and net benefits. High AMLPIs in AML patients were indicative of unfavorable prognostic outcomes. Immune analyses revealed that the high-AMLPI samples exhibit higher expression of HLA-family genes and immune checkpoint genes (including PD1 and CTLA4), along with lower T cell infiltration and higher macrophage infiltration. Genetic variation analyses revealed that the high-AMLPI samples associate with adverse variation events, including TP53 mutations, secondary NPM1 co-mutations, and copy number deletions. Biological interpretation indicated that ALDH2 and SPATS2L contribute significantly to AML patient survival, and their abnormal expression correlates with DNA methylation at cg12142865 and cg11912272. Drug response analyses revealed that different AMLPI samples tend to have different clinical selections, with low-AMLPI samples being more likely to benefit from immunotherapy. Finally, to facilitate broader access to our findings, a user-friendly and publicly accessible webserver was established and available at http//bioinfor.imu.edu.cn/amlpi. This server provides tools including TME-related AML driver genes mining, AMLPI construction, multi-dimensional validations, AML patients risk assessment, and figures drawing.