mTOR Modulation Affects Galectin-1 Expression in KMT2A -rearranged Acute Lymphoblastic Leukemia Cells

Background/Aim: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Among its genetic subtypes, KMT2A (formerly MLL)-rearranged ALL (KMT2Ar-ALL) is associated with poor outcomes. Immunotherapy approaches are being studied and used in KMT2Ar-ALL; however, there is evidence that leukemic cells can escape immune control. Our previous study identified Galectin-1, an immune checkpoint protein, as highly expressed in KMT2Ar-ALL, suggesting it as a potential therapeutic target. To date, the exact mechanism of Galectin-1 regulation in KMT2Ar-ALL is unknown. Therefore, the present study aimed to investigate the potential involvement of the mTOR signaling pathway in the regulation of Galectin-1 expression in KMT2Ar-ALL. Materials and Methods: The study employed both in silico and in vitro approaches: gene expression data from B-cell acute lymphoblastic leukemia subtypes were analyzed bioinformatically, while four leukemia cell lines (RS4;11, SEMK2, SUP-B15, and NB-4) were treated with the mTOR inhibitor everolimus to evaluate its effect on Galectin-1 expression at the mRNA and protein levels, using qPCR and immunoblotting. Transcription factor binding on the LGALS1 promoter was assessed with computational tools. Results: Galectin-1 mRNA and protein were selectively upregulated in KMT2Ar-ALL cells, and inhibition of the mTOR pathway with everolimus modulated Galectin-1 expression in these cells. A novel putative transcription factor, SP1, was proposed, which may bind to the Galectin-1 promoter and can be regulated by the mTOR pathway. Conclusion: Targeting mTOR signaling contributes to the regulation of Galectin-1 immune checkpoint activity in KMT2Ar-ALL. Inhibition of mTOR may represent a potential therapeutic strategy to overcome immune evasion in this leukemia subtype.