Effect of FLT3 ligand on the gene expression of TIM-3, HIF1-α, and TNF-α in an acute myeloid leukemia cell line.

Abstract

Background: Acute Myeloid Leukemia (AML) pathogenesis is driven by the dysregulation of various cell signaling pathways, including the FMS-Like Tyrosine Kinase 3 (FLT3) pathway and its ligand (FLT3L). These pathways play a critical role in promoting cell survival, proliferation, and resistance to apoptosis, contributing to leukemogenesis. In this study, we investigated the effects of FLT3L on the expression of key genes associated with immune regulation, hypoxia, and inflammation-TIM-3, HIF-1α, and TNF-α-in the THP-1 cell line, a well-established model for AML research.

Methods: THP-1 cells were cultured under standard conditions and treated with varying concentrations of FLT3L, alongside PMA as a positive control. Quantitative RT-PCR was employed to measure the expression levels of TIM-3, HIF-1α, and TNF-α genes after 48 h of treatment.

Results: Our findings demonstrated that specific concentrations of FLT3L significantly upregulated the expression of TIM-3, HIF-1α, and TNF-α in THP-1 cells. This suggests that FLT3L not only influences cell proliferation and survival but also modulates pathways related to immune evasion, hypoxia adaptation, and inflammatory responses, which are hallmarks of leukemia progression.

Conclusion: These results highlight the pivotal role of FLT3L in regulating the expression of genes associated with AML pathogenesis, particularly those involved in hypoxia (HIF-1α), immune checkpoint regulation (TIM-3), and inflammation (TNF-α). The findings underscore the potential of targeting the FLT3 pathway as a therapeutic strategy in AML. Further studies are warranted to elucidate the underlying molecular mechanisms and explore their clinical implications for improving patient outcomes.