The Expression And Role Of The IL-37 In Acute Myeloid Leukemia

Objective: To investigate the expression and the clinical significance of the interleukin-37 in acute myeloid leukemia(AML)and to explore the potential mechanism.Methods: Bone marrow and peripheral blood samples were collected from 108 AML patients,including 51 cases of initial onset,45 cases of remission,and 12 cases of refractory relapse,and 20 healthy human bone marrow and peripheral blood serum from 55 healthy physical examination personnel were used as controls.The expression of IL-37 and its subtypes mRNA in bone marrow samples was detected by PCR and the expression levels of IL-37 and IL-6 in peripheral blood samples were detected by enzyme-linked immunosorbent assay(ELISA).The correlation between the expression levels of IL-37 and IL-6 in AML patients and the relationship between the expression levels of IL-37 and the clinicopathological characteristics of AML patients was analyzed.Human leukemia cell lines HL-60,K562 and peripheral blood mononuclear cells(PBMC)extracted from newly diagnosed AML patients were cultured in vitro,and different concentrations of recombinant human IL-37 protein(Rh IL-37)was added,respectively.The effect of RhIL-37 protein on the proliferation of AML cells was detected by CCK-8 kit,and the effect of RhIL-37 protein on the expression level of IL-6 in AML cells was detected by ELISA.Results: Compared with the control group,IL-37 mRNA expression was decreased in AML patients,but the difference was not statistically significant(P﹥0.05),and two subtypes of IL-37 b and IL-37 d were expressed in bone marrow from AML patients.Importantly,IL-37 expression levels were down-regulated in the serum of newly diagnostic AML patients compared with the control group(P﹤0.01)and recovered in AML patients in remission after treatment(P﹤0.01).According to NCCN2011 guidelines,the prognostic stratification of newly diagnosed AML patients revealed that the expression level of IL-37 was higher in the favorable group than in the intermediate and poor prognosis groups(P﹤0.05).Moreover,the expression level of IL-37 was associated with nucleophosmin 1(NPM1)mutation in AML patients,and the NPM1 mutation rate was higher in the IL-37 high expression group(P ﹤ 0.05).Further analysis revealed that IL-37 expression was significantly negatively correlated with IL-6 expression in peripheral blood serum of AML patients(r =﹣0.3682,P﹤0.01).RhIL-37 protein inhibited the proliferation of HL-60 and K562 cells(P﹤0.01),but did not affect the expression level of IL-6(P﹥0.05).RhIL-37 protein significantly inhibited IL-6 secretion in PBMCs from AML patients(P﹤0.001).Conclusion: Low expression of IL-37 may be an important factor in the prognosis of AML patients,and may be involved in AML development by regulating IL-6,indicating that IL-37 is expected to provide an innovative research strategy for AML pathogenesis and therapy.