IL-37 and SIGIRR downregulation linked to poor treatment response in de novo Acute Myeloid Leukemia
Background
Acute Myeloid Leukemia (AML) is a heterogeneous hematologic malignancy with variable treatment outcomes. Despite advances, many patients experience refractory disease or relapse, highlighting the need for novel prognostic biomarkers. Interleukin-37 (IL-37) is an anti-inflammatory cytokine with emerging roles in immune regulation and tumor biology. Its interaction with the single immunoglobulin IL-1-related receptor (SIGIRR) modulates inflammatory signaling pathways, which may influence leukemogenesis. The clinical significance of this IL-37/SIGIRR axis in AML, particularly its association with treatment response, remains underexplored.
Study Design
This observational study enrolled 50 newly diagnosed adult patients with AML and 50 age- and sex-matched healthy controls. Researchers quantified expression levels of IL-37 and SIGIRR mRNA using reverse transcription quantitative polymerase chain reaction (RTqPCR). The primary objective was to explore associations between IL-37 and SIGIRR expression with clinical characteristics, molecular mutations, and treatment outcomes, specifically focusing on complete remission versus refractory disease.
Results
Both IL-37 and SIGIRR mRNA expression levels were significantly downregulated in patients with Acute Myeloid Leukemia (AML) compared to healthy controls (p = 0.011 and p < 0.001, respectively). This suggests a systemic alteration in this anti-inflammatory pathway in AML. Further analysis revealed a strong correlation with treatment response: patients with refractory disease exhibited significantly lower expression levels of both markers compared to those who achieved complete remission. For IL-37, this difference was significant (p = 0.006), and for SIGIRR, it was highly significant (p < 0.001).
Key Findings
- IL-37 mRNA expression was significantly downregulated in AML patients vs. healthy controls (p = 0.011).
- SIGIRR mRNA expression was significantly downregulated in AML patients vs. healthy controls (p < 0.001).
- Refractory AML patients had significantly lower IL-37 expression than those in complete remission (p = 0.006).
- Refractory AML patients had significantly lower SIGIRR expression than those in complete remission (p < 0.001).
Why It Matters
This study identifies the IL-37/SIGIRR axis as a potential prognostic biomarker for Acute Myeloid Leukemia (AML), offering a new tool for predicting treatment response. For clinicians, monitoring IL-37 and SIGIRR expression could help stratify AML patients at diagnosis, potentially guiding more aggressive or alternative therapeutic strategies for those with downregulated expression. This finding also opens avenues for novel immunomodulatory therapeutic strategies in AML by targeting this pathway, moving beyond traditional chemotherapy. While still preclinical, these results suggest that restoring or enhancing IL-37/SIGIRR signaling could improve outcomes, though a usable clinical protocol is still far off.
acute myeloid leukemia
aml
il-37
sigirr
biomarker
prognosis