Decoding the diagnostic biomarkers of mitochondrial dysfunction related gene variants in pediatric T cell acute lymphoblastic leukemia.

Mitochondrial dysfunction is crucial in the pathogenesis and drug resistance of pediatric T-cell acute lymphoblastic leukemia (T-ALL), a malignant hematological disorder with unrestrained proliferation of immature T-cells. Therefore, the primary objective of this study is to elucidate the role of mitochondrial dysfunction-related differentially expressed genes (MDRDEGs) in pediatric T-ALL and to establish a diagnostic model based on the MDRDEGs. We obtained datasets from GEO on pediatric T-ALL patients and healthy controls. A comprehensive list of 843 mitochondrial dysfunction-related genes (MDRGs) was compiled from GeneCards database and PubMed literature. Subsequently, we identified significant MDRDEGs, also, performed functional enrichment and analysis immune infiltration analysis. Additionally, A mitochondrial dysfunction-based signature was created to predict pediatric T-ALL. The mRNA-miRNA and mRNA-TF Regulatory Network were constructed, and the molecular distributions of key genes were calculated. There were 8029 differentially expressed genes (DEGs) in pediatric T-ALL compared to controls. Intersecting these DEGs with MDRGs yielded 284 MDRDEGs. Enrichment analyses revealed that these MDRDEGs were involved in oxidative stress response, cellular respiration, mitochondrial inner membrane composition, and protein complexes. GSEA and GSVA highlighted significant enrichment in NF-κB and JAK-STAT pathways. The intersection of LASSO regression and RF algorithms highlighted two pivotal genes: RNLS and ULK1. Validation dataset demonstrated our diagnostic model's high accuracy. In conclusion, this study systematically investigated MDRDEGs' roles in pediatric T-ALL and constructed an effective diagnostic model. The findings provided new potential biomarkers for early diagnosis and therapeutic targets for pediatric T-ALL, offering promising directions for future research.