The IRF2-INPP4B pathway is activated in CD4+ T cells and aggravates acute myeloid leukemia development by inhibiting apoptosis.

Abstract

Background: Interferon-regulatory factor 2 (IRF2)/inositol polyphosphate 4-phosphatase B (INPP4B) is essential for the differentiation of immune T cells. However, the regulatory mechanism of IRF2/INPP4B signaling pathway on apoptosis of acute myeloid leukemia (AML) cells remains unclear. Thus, this study intended to investigate the function and mechanism of IRF2/INPP4B in the development of AML.

Methods: CD4+ T cells were isolated from peripheral blood and identified using flow cytometry. Apoptosis of AML cell line HL60 and the ration of Th1/Th2 were analyzed by flow cytometry. The mRNA expression of IRF2 was detected by quantitative real-time PCR method. Western blot was used to detect the protein accumulation of IRF2, INPP4B, JAK2, p-JAK2, STAT3, p-STAT3, and caspase 3. The contents of IL-4 and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA) kits.

Results: We found that IRF2 and INPP4B were highly expressed in AML-derived CD4+ T cells. Further results indicated that CD4+ T cells promoted HL60 cell apoptosis. Moreover, we found that downregulation of IRF2 promoted HL60 cell apoptosis by regulating Th1/Th2 ratio. In addition, we revealed that overexpression of IRF2 activated JAK2/STAT3 signaling pathway and downregulated caspase 3 expression.

Conclusion: We demonstrated that the IRF2-INPP4B signaling in CD4+ T cells activated the JAK2/STAT3 signaling pathway and downregulated caspase 3 expression, causing inhibition on AML cell apoptosis to aggravate AML development. This study proposes a novel regulatory mechanism in AML development, suggesting that the IRF2/INPP4B pathway might influence the JAK2-STAT3 signaling pathway, adding a new layer to our understanding of the complex interplay of these pathways in AML development.