Identification and experimental validation of mitochondria pathway related genes in acute myeloid leukemia.

BACKGROUND

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by heterogeneity, poor prognosis, and limited biomarkers for risk prediction. Mitochondria pathway related genes (MPRGs), as central regulators of cellular metabolism and immune microenvironment dynamics, may provide useful information for prognostic assessment and biological characterization in AML.

METHODS

MPRGs were obtained from the MitoCarta3.0 database. Univariate Cox and Kaplan-Meier methods were conducted to analyze their prognostic relevance. LASSO penalized regression followed by stepwise multivariate Cox analysis yielded an optimal gene panel in the TCGA-LAML dataset. External validation was performed across three GEO datasets (GSE10358, GSE106291, GSE71014). Finally, the role of UCP2 was examined in vitro by assessing UCP2 knockdown effects on MOLM-13 cell behavior.

RESULTS

A prognostic signature comprising seven MPRGs (UCP2, FAM162A, ACCS, HSD1, ACSF2, PPIF, and SDHA) was established. High-risk patients exhibited significantly shorter survival. The MPRGs risk score served as an independent predictor of prognosis. Moreover, elevated risk scores correlated with heightened immune checkpoint molecule expression and an immunosuppressive tumor microenvironment. UCP2 knockdown attenuated both proliferative capacity and migratory potential in MOLM-13 AML cells.

CONCLUSION

In summary, the MPRG-based signature provides independent prognostic value in AML and reflects its association with an immunosuppressive microenvironment. These findings provide additional evidence that mitochondrial pathway-related genes are associated with AML prognosis and immune microenvironment features. UCP2 may represent a biologically relevant candidate gene in AML, although further mechanistic and clinical validation is required.