Investigating the Immunological Significance of TGFB1 and MDA in ALL TME

Abstract

Background: The tumor microenvironment (TME) in acute lymphoblastic leukemia (ALL) significantly shapes disease progression and therapeutic responses. This study investigates the regulatory role of bone marrow mesenchymal stem cell (BMSC)-released transforming growth factor beta-induced factor homeobox 1 (TGIF1) on myeloid nuclear differentiation antigen (MNDA) expression, immune infiltration, and patient prognosis in ALL.

Materials and Methods: A comprehensive bioinformatics approach analyzed gene expression, protein interactions, and immunological correlations. Differential expression, enrichment analyses, and protein-protein interaction (PPI) networks identified key regulatory genes. The relationship between TGIF1 and MNDA and their immunological impact were assessed through correlation and survival analyses.

Results: Differential analysis identified 424 differentially expressed genes (DGEs). The PPI network and Cox regression highlighted MNDA as a significant gene associated with patient outcomes. High MNDA expression correlated with better survival (P=0.013), and ROC analysis demonstrated its strong prognostic potential (AUC=0.934). GSEA indicated MNDA involvement in immune-related signaling pathways. Immune infiltration analyses linked MNDA expression to seven immune cell types. Additionally, transcription factor TGIF1 positively correlated with MNDA expression, significantly upregulated in healthy BMSCs but downregulated in ALL samples.

Conclusion: BMSC-derived TGIF1 positively regulates MNDA expression, influencing immune infiltration and ALL progression. Targeting the interplay between TGIF1 and MNDA introduces a new molecular strategy for managing ALL.