IL-37 Was Involved in Progress of Acute Myeloid Leukemia Through Regulating IL-6 Expression

Background: Interleukin-37, which was discovered in 2000, is a natural suppressor of immune and inflammatory responses. Recent studies reported that IL-37 was abnormally expressed in several tumor patients, including those with hepatocellular carcinoma, gastric cancer, lung cancer, colon cancer, epithelial ovarian cancer, and multiple myeloma. However, the expression and potential function of IL-37 in leukemia remain unknown. Objective: The aim of this study was to evaluate IL-37 as a prognostic factor and its possible mechanism of action. Methods: Polymerase chain reaction products were analyzed by agarose gel electrophoresis and were purified and subsequently sequenced by a genetic testing laboratory. Human PBMC was purified from whole blood samples by using Ficoll-Paque PLUS. The concentrations of human IL-37 and human IL-6 were measured using enzyme-linked immunosorbent assay (ELISA) kits. Results: IL-37, especially isoform b and d, was expressed in the bone marrow of AML, CML, ALL, and CLL. Importantly, IL-37 expression was downregulated in newly diagnosed AML patients and restored in patients in complete remission. Moreover, a significant association was found between IL-37 expression and NPM1 mutation or possible prognosis evaluated by karyotype and gene mutation. Further analysis revealed that IL-37 expression was negatively correlated with IL-6 expression. With regard to the mechanism, recombinant human IL-37 could suppress IL-6 expression stimulated by LPS in PBMC of AML patients. Conclusion: Our study suggested that IL-37 may be an important prognostic factor in AML and is involved in AML via the IL-6 signaling pathway, indicating that IL-37 is an innovative research strategy for AML pathogenesis and therapy.

Automated summary

IL-37, particularly isoform b and d, was found to be expressed in the bone marrow of various types of leukemia. Downregulation of IL-37 expression was observed in newly diagnosed AML patients, but restored in complete remission, showing a significant association with NPM1 mutation and prognosis. IL-37 expression was also negatively correlated with IL-6 expression and could suppress IL-6 expression in AML patients, indicating a potential therapeutic strategy for AML.