OBJECTIVE: To investigate the characteristics of gene mutations in patients with myelodysplastic syndromes (MDS) and its prognostic significance. METHODS: High-throughput sequencing was used to detect 34 blood tumor-related genes in 210 patients with MDS, and the relationship with the revised International Prognostic Scoring System (IPSS-R) and the impact on prognosis of the patients were analyzed. RESULTS: Among the 210 MDS patients, 142 cases (67.6%) showed mutations, and the first six genes with the highest mutation detection rate were ASXL1(20.5%), TET2(17.1%), U2AF1(14.3%), DNMT3A (11.9%), TP53(10.5%) and RUNX1(10.0%). The gene mutation rate of the patients in IPSS-R relatively high-risk group was higher than those in relatively low-risk group (P=0.001). Both TP53 and BCOR genes showed higher mutation rates in the higher risk group than in the lower risk group (P<0.05). Survival time of the patients in TP53 mutant group was lower than those in non-mutant group (P<0.001), survival time of patients in SF3B1 mutant group was higher than those in non-mutant group (P=0.018). According to the number of gene mutations, the patients could be divided into groups with 0-1, 2 and ≥3 gene mutations, and the median OS of the three groups were not reached, 43 and 27 months, respectively (P=0.004). The Multivariate analysis showed that the increasing number of gene mutations and TP53 mutation was the independent risk factors affecting prognosis of the patients, while SF3B1 mutation was the independent protective factor for the prognosis of the patients. CONCLUSION The gene mutation rate was higher in MDS patients. And the increasing numbers of gene mutation, TP53 and SF3B1 were the influence factors of prognosis in the patients.
Genes, Regulator ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Myelodysplastic Syndromes/genetics* ; Prognosis

OBJECTIVE: To study the effect of SMO inhibitor (Jervine) on proliferation, apoptosis and cell cycle of MDS cell line MUTZ-1, and its mechanism. METHODS: The effect of different concentrations Jervine on proliferation of MUTZ-1 cells was detected by CCK-8 method. Apoptosis and cell cycle of MUTZ-1 cells were detected by flow cytometry. Western blot was used to detect the changes of Shh signaling pathway effecting proteins BCL2 and CyclinD1. The expression levels of Smo and Gli1 gene were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). RESULTS: Jervine inhibited MUTZ-1 cell proliferation in a concentration dependent manner (24 h, r=-0.977), the apoptosis rate of MUTZ-1 cells increased with the enhancement of concentration of Jervine in MUTZ-1 cells (P＜0.001), the cell proportion of G phase increased and the cell number of S phase decreased with enhancement of concentration (P＜0.001). The result of RT-qPCR and Western blot showed that the expression of Smo, Gli1 mRNA and BCL2, CyclinD1 proteins decreased (P＜0.05). CONCLUSION SMO inhibitor can effectively inhibit the growth of MDS cell line MUTZ-1 improve the cell apoptosis and induce cell cycle arrest. Its action mechanism may be related with dowm-regulating the expression of BCL2 and CyclinD1.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Hedgehog Proteins ; Humans ; Myelodysplastic Syndromes ; Signal Transduction ; Veratrum Alkaloids