Abstract：
Acute myeloid leukemia (AML) is a malignant disorder of hemopoietic stem cells. AML can escape immunosurveillance of natural killer (NK) by gene mutation, fusions and epigenetic modification. The mechanism of AML immune evasion is not clearly understood. Here we show that CD48 high expression is a favorable prognosis factor that is down-regulated in AML patients, which can help AML evade from NK cell recognition and killing. Furthermore, we demonstrate that CD48 expression is regulated by methylation and that a hypomethylating agent can increase the CD48 expression, which increases the NK cells killing in vitro. Finally, we show that CD48 high expression can reverse the AML immune evasion and activate NK cells function in vivo. The present study suggests that a combination the hypomethylating agent and NK cell infusion could be a new strategy to cure AML.
摘要：
急性髓性白血病（AML）是造血干细胞的恶性疾病。AML可以通过基因突变逃避自然杀伤（NK）的免疫监视，融合和表观遗传修饰。AML免疫逃避的机制尚不清楚。在这里，我们显示CD48高表达是AML患者中下调的有利预后因素，这可以帮助AML逃避NK细胞的识别和杀伤。此外，我们证明CD48表达受甲基化调节，低甲基化剂可以增加CD48表达，这增加了NK细胞在体外的杀伤。最后,我们证明CD48高表达可以逆转AML的免疫逃避并激活体内NK细胞的功能。本研究表明，低甲基化剂和NK细胞输注的组合可能是治疗AML的新策略。
