临床发现感染后极少数急性髓系白血病(Acute Myeloid Leukemia,AML)患者可获得暂时缓解。我们研究了细胞识别病原体的重要受体，Toll样受体(Toll-Like Receptor, TLR)，对AML细胞的作用。发现激活TLR8/MyD88信号通路能明显诱导部分AML细胞的分化,并抑制AML细胞的生长，该研究发表于《leukemia》2014年电子版。随后发现细菌脂多糖能显著促进该分化作用。这表明细菌脂多糖激活的TLR4/MyD88途径可能增强了经TLR8/MyD88途径的诱导分化作用。单链病毒RNA也能激活TLR8。我们提出假说，在AML患者出现细菌和病毒感染后，可能同时激活TLR4/MyD88及TLR8/MyD88信号通路，可能诱导部分特定免疫表型的AML细胞分化，并使AML获得暂时缓解。因此，深入研究感染后人体对AML细胞的作用，可能探索出诱导AML缓解的新方法。

Spontaneous remission in the course of acute myeloid leukemia (AML) is observed very rarely after severe systemic infections. We investigated the effect of the toll-like receptor (TLR) ligands on AML cells. The differentiation of AML cells was induced by R848 through TLR8/MyD88 signal pathway. The results was published on the journal “leukemia”. Later, we found that LPS promote the differentiation of AML cells induced by R848. It suggest that LPS may enhance the TLR8/MyD88 dependent pathway differentiation through TLR4/MyD88 signal pathway. ssRNA of virus is also a ligand of TLR8. We assume that spontaneous remission of AML may happen after the activation of TLR4/MyD88 and TLR8/MyD88 pathway by infection of bacteria and virus. So, to investigate the mechanisms of AML cells after infection may help to find a new strategy to treat AML.

通过本项目的研究证实，TLR7/8的激动剂R848能诱导急性髓系白血病患者原代白血病细胞分化和凋亡。高浓度(25ug/ml)R848比低浓度(10ug/ml)R848有更好的诱导分化和凋亡效果。LPS联合R848诱导分化及凋亡的效果更明显。对于不同类型的急性髓系白血病细胞，R848的作用效果有一定的差别，尤其对M4eo的诱导分化和凋亡效果更好。但因时间有限，初发的急性髓系白血病患者数量有限，还不能肯定对哪种遗传学改变的AML效果更好，初步发现对伴inv(16;16)的AML可能效果更好。R848可通过TLR/MyD88途径提高NK细胞的活性，并促进对急性髓系白血病患者原代白血病细胞的杀伤作用。应用其它促进NK细胞活性的办法也能促进NK细胞的活性，促进对AML细胞的杀伤作用。联合诱导分化凋亡疗法和免疫学方法可能成为治疗急性髓系白血病的新的治疗方向。