[Analysis of the Effect of TET2 Mutation and SNP on Clinical Characteristics and Prognosis of AML Patients].

OBJECTIVE: To evaluate the clinical significance of TET2 mutation(TET2mut) and SNP in adult acute myeloid leukemia (AML) and its effect on prognosis. METHODS: A total of 24 genes, including TET2, FLT3-ITD and NPM1, were detected in 124 adult AML patients using second-generation sequencing technology, and their clinical characteristics and effect on prognosis of patients were analyzed. RESULTS: A total of 25 TET2 gene mutations were detected in 124 AML patients, the mutation rate was 20.2%, there were 75 cases of TET2 single nucleotide polymorphisms(SNP), accounting for 60.5%. There were 47 cases of SNPrs2454206(G>A), accounting for 37.9%. Compared with TET2 wild-type(TET2wt) patients, TET2mut patients were mostly elderly. TET2SNP was commonly seen in male, with statistically significant differences (P＜0.05). SNP rs2454206 had no significant correlation with sex and age (P＞0.05). However, the analysis found that the complete remission rate of 1 course and the total complete rate (CR) of patients with TET2AG/GG were both obviously superior to those with TET2AA (P＜0.05). In the univariate analysis, the overall survival(OS) rate of the patients with TET2mut was lower than that of patients with TET2wt, and the event free survival (EFS) rate was higher than that of TET2wt patients, but the difference was not statistically significant (P＞0.05).The 1-year OS rate and EFS rate of the patients with TET2AA were significantly lower than those of the patients with TET2AG/GG (P＜0.05). Multivariate analysis showed that TET2AA was an independent risk factor for OS and EFS in AML patients. CONCLUSION: TET2 SNPrs2454206(G＞A) commonly appears in patients with acute myeloid leukemia, and these patients have the better response to chemotherapy and a better prognosis.

[Proventive and Therapentic Effects of Endothelial Progenitor Cells on Monocrotaline-Induced Hepatic Vein Occlusion Disease].

OBJECTIVE: To investigate the preventive and therapeutic effects of endothelial progenitor cells on monocrotaline-induced hepatic vein occlusion disease in mice. METHODS: C57BL/6 mice were randomly divided into 3 groups: saline group (n=15), monocrotaline group (n=15), and endothelial progenitor cell infusion group (n=15). Liver function (TBIL, ALT, AST), liver index, and serum levels of TNF-α and IL-6 were measured on the 8th day after intragastric administration. Hepatic sinusoidal endothelial cells, hepatic central venous endothelial cells and hepatocytes were observed by both HE and immunohistochemical staining. Hepatic fibrosis was observed by Masson's trichrome staining. RESULTS: By the light microscopy, the liver of the monocrotaline group showed moderate to the severe injuries of hepatic sinusoidal and central venous endothelial cells, and hepatic venous congestion. Masson staining showed moderate to severe hepatic fibrosis of central vein and hepatic sinus. In the endothelial progenitor cell group, hepatic sinusoidal and central venous endothelial cell injuries, and the fibrosis of central hepatic vein and hepatic sinus were mild to moderate. Hepatic venous congestion was reduced in comparison with that in the mice of the monocrotaline group. Compared with the endothelial progenitor cell group, the liver index was higher, the liver function was more abnormal, and the serum expression levels of TNF-α and IL-6 were higher in the monocrotaline group. CONCLUSION: The monocrotaline-induced damage of hepatic sinusoidal and central venous endothelial cells is an linitiating factor for hepatic vein occlusive disease. Infusion of endothelial progenitor cells can play a role in preventing and treating hepatic vein occlusion.

[Effects of liver sinusoid endothelial cell injury in mouse hepatic veno-occlusive disease].

This study was purposed to investigate the role of monocrotaline-inducing mouse liver sinusoid endothelial cell (SEC) injury in hepatic veno-occlusive disease. BALB/c mice were randomly divided into 2 groups: control group and monocrotaline group, mice were orally administrated with normal saline or monocrotaline with concentration of 200 mg/kg at days 0, 1, 2, respectively. At days 3, 4, 6, 8 and 10 after oral administration with normal saline or monocrotaline, the liver function (ALT, TBIL, AKP) and liver index were examined, and the percentage of activated platelets were detected by flow cytometry. The SEC, vascular endothelial cells and hepatic fibrosis were observed by staining with hematoxylin-eosin and Masson. Transmission electron microscopy was used to observe sinusoidal endothelial cell damage and platelet adhesion. The results showed that compared with control group, mice in monocrotaline group were characterized by severe damage of SEC, numbers of platelet aggregation and adhesion, central number and sinusoidal fibrosis. The percentage of activated platelets and liver index increased (P < 0.05). The characterization of portal hypertension was presented later, such as dysfunction of liver and ascites. It is concluded that SEC injury induced by monocrotaline may be the first step of hepatic veno-occlusive disease, and this kind of SEC injury is self-limiting, but fibrosis is always observed.