Acute myeloid leukemia (AML) is a fatal disease characterized by the accumulation of immature myeloid blasts in the bone marrow (BM). Cytokine provide signals for leukemia cells to improve their survival in the BM microenvironment. Previously, we identified interleukin-33 (IL-33) as a promoter of cell survival in a human AML cell line and primary mouse leukemia cells. In this study, we report that the cell surface expression of IL-33–specific receptor, Interleukin 1 Receptor Like 1 (IL1RL1), is elevated in BM cells from AML patients at diagnosis, and the serum level of IL-33 in AML patients is higher than that of healthy donor controls. Moreover, IL-33 levels are found to be positively associated with IL-6 levels in pediatric patients with AML. In vitro, IL-33 treatment increased IL-6 mRNA expression and protein level in BM and peripheral blood (PB) cells from AML patients. Evidence was also provided that IL-33 inhibits cell apoptosis by activating p38 mitogen-activated protein kinase (MAPK) pathway using human AML cell line and AML patient samples. Finally, we confirmed that IL-33 activated IL-6 expression in a manner that required p38 MAPK pathway using clinical AML samples. Taken together, we identified a potential mechanism of IL-33–mediated survival involving p38 MAPK in pediatric AML patients that would facilitate future drug development.

急性髓细胞性白血病（AML）是一种致命疾病，其特征是未成熟的髓母细胞在骨髓（BM）中积累。细胞因子为白血病细胞提供信号，以改善其在BM微环境中的存活率。以前，我们将白介素33（IL-33）鉴定为人类AML细胞系和原代小鼠白血病细胞中细胞存活的启动子。在这项研究中，我们报告了在诊断时来自AML患者的BM细胞中IL-33特异性受体白介素1受体样1（IL1RL1）的细胞表面表达升高，而在AML患者中血清IL-33的表达升高高于健康的捐献者对照。此外，发现小儿AML患者中IL-33水平与IL-6水平呈正相关。体外，IL-33治疗可增加AML患者的BM和外周血（PB）细胞中IL-6 mRNA表达和蛋白水平。还提供证据表明，IL-33通过使用人AML细胞系和AML患者样品激活p38丝裂原激活的蛋白激酶（MAPK）途径来抑制细胞凋亡。最后，我们证实使用临床AML样品，IL-33以要求p38 MAPK途径的方式激活了IL-6表达。综上所述，我们确定了小儿AML患者中由p38 MAPK介导的IL-33介导的生存的潜在机制，这将促进未来的药物开发。