The IRF2-INPP4B Pathway Aggravates Acute Myeloid Leukemia.

OBJECTIVE: Interferon-regulatory factor 2 (IRF2) and inositol polyphosphate 4-phosphatase B (INPP4B) are indispensable for differentiating immune T-cells, but the regulatory principle of the IRF2-INPP4B signaling channel in the apoptosis of acute myeloid leukemia (AML) cells remains unclear. This work investigates the function and regulatory principle of IRF2-INPP4B signaling in the progression of AML. MATERIALS AND METHODS: CD4(+) T-cells were extracted from peripheral blood and characterized via flow cytometry. Flow cytometry was used to estimate apoptosis in the HL60 AML cell line and determine the Th1/Th2 cell ratio. Quantitative real-time polymerase chain reaction was used to measure IRF2 mRNA. Western blotting was performed to evaluate the protein levels of IRF2, INPP4B, JAK2, p-JAK2, STAT3, p-STAT3, and caspase 3. Interleukin-4 and interferon gamma concentrations were determined using enzyme-linked immunoadsorption assay kits. RESULTS: We discovered that levels of IRF2 and INPP4B were high in AML-derived CD4(+) T-cells. Furthermore, CD4(+) T-cells encouraged HL60 cell apoptosis. Downregulation of IRF2 encouraged HL60 cell apoptosis via alterations in the Th1/Th2 ratio while the overexpression of IRF2 stimulated the JAK2-STAT3 signaling channel and downregulated caspase 3. CONCLUSION: We revealed that IRF2-INPP4B signaling in CD4(+) T-cells stimulated the JAK2-STAT3 signaling channel and downregulated caspase 3, reducing AML cell apoptosis and aggravating AML progression. This work highlights an important regulatory principle concerning AML progression, as the IRF2-INPP4B pathway might impact the JAK2-STAT3 signaling channel. The findings contribute to our knowledge of the complicated interplay of these pathways in AML.