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

Area of Science:

• Hematologic Malignancies
• Molecular Biology
• Cancer Genomics

Background:

• Acute myeloid leukemia (AML) presents significant challenges due to its heterogeneity, poor prognosis, and lack of reliable biomarkers for risk stratification.
• Mitochondria pathway related genes (MPRGs) play crucial roles in cellular metabolism and immune microenvironment regulation, offering potential for prognostic assessment in AML.

Purpose of the Study:

• To identify and validate a prognostic gene signature based on MPRGs for acute myeloid leukemia (AML).
• To investigate the association between the MPRG-based signature and the tumor immune microenvironment in AML.
• To explore the functional role of UCP2 in AML cell behavior.

Main Methods:

• MPRGs were sourced from the MitoCarta3.0 database.
• Prognostic relevance was assessed using univariate Cox and Kaplan-Meier analyses.
• A seven-gene prognostic signature was developed using LASSO and stepwise multivariate Cox regression in the TCGA-LAML dataset and validated on three GEO datasets.
• The in vitro role of UCP2 was evaluated by assessing knockdown effects on MOLM-13 cell proliferation and migration.

Main Results:

• A seven-MPRG prognostic signature (UCP2, FAM162A, ACCS, HSD1, ACSF2, PPIF, SDHA) was established, with high-risk patients showing significantly shorter survival.
• The MPRG risk score independently predicted prognosis and correlated with increased immune checkpoint molecule expression and an immunosuppressive tumor microenvironment.
• Knockdown of UCP2 in MOLM-13 cells reduced their proliferative and migratory capacities.

Conclusions:

• The MPRG-based signature offers independent prognostic value in AML and is linked to an immunosuppressive microenvironment.
• These findings reinforce the association between MPRGs, AML prognosis, and immune microenvironment characteristics.
• UCP2 emerges as a potential biologically relevant candidate gene for AML, warranting further investigation and clinical validation.