OBJECTIVETo investigate the therapy and efficacy after remission of patients with acute myeloid leukemia (AML).

METHODSThe clinical data of 110 patients diagnosed as AML treated from 2008 to 2013 were analyzed retrospectively. According to different consolidation therapy regimens, the patients were divided into 4 groups:1 ID-Ara-C group, 2 ID-Ara-C group, 3-4 ID-Ara-C group, allogeneic hematopoietic stem cell transplantation (allo-HSCT) group. The disease-free survival (DFS) and overall survival (OS) were analyzed retrospectovely.

RESULTS110 patients were completely remittend by 1-2 couses. The median follow-up time was 26.8 months, 35 cases relapsed and 58 cases died, the median DFS and OS were 20.5 and 26.8 months. The 3-year DFS of 1, 2, 3-4 ID-Ara-C and allo-HSCT groups were 0%, 36.1%, 37.5% and 67.9% respectively. The 5-year DFS of 1, 2, 3-4 ID-Ara-C and allo-HSCT groups were 0%, 30.1%, 37.5% and 63.0%. The 3-year OS rates of 1, 2 ID-Ara-C groups, 3-4 ID-Ara-C group and allo-HSCT group were 24.0%, 36.0%, 58.3% and 67.8%. The 5-year OS of 1, 2 ID-Ara-C grous, 3-4 ID-Ara-C and allo-HSCT group were 24.0%, 36.0%, 58.3% and 67.8% respectively. The 5-year OS rates of 1 ID-Ara-C group, 2 ID-Ara-C group, 3-4 ID-Ara-C group were 0%,30.0%,35.0% and 62.9% respectively. The multifactor analysis indicated that the courses of ID-Ara-C and allo-HSCT were independent risk factors for DFS and OS.

CONCLUSION≥2 ID-Ara-C regimen may be used as one regimen of consolidation therapy for patients with AML after remission.

OBJECTIVETo investigate the value of p15, DAPK, SOCS1 and FHIT genes combined detection in the early diagnosis and prognosis evaluation of patients with myelodysplastic syndrome(MDS).

METHODSThe methylation-specific PCR (MSP) was used to detect the methylation of the above-mentioned 4 genes in 67 patients with MDS. The value of 4 gene combined detection in the early diagnosis and prognosis evaluation of patients with MDS was compared and anazlyzed.

RESULTSThe methylation rates of p15, DAPK, SOCS1 and FHIT genes in 67 patients with MDS were 37.3%, 35.8%, 47.8% and 52.2%, respectively, which were significantly higher than those in control group (P<0.05). The accordance rates of p15, DAPK, SOCS1 and FHIT single detection for diagnosis of MDS were 37.3%,35.8%,47.8% and 52.2%, respectively, meanswhile the accordance rate of above-mentioned 4 gene combined detection for diagnosis of MDS was 82.1%, which was significantly higher than that of single gene detection(P<0.001). The methylation of ≥2 genes in relatively high risk group was significantly higher than that in relatively low risk group (P<0.05). The median survival time of MDS patients was 18(13.3, 22.7) months; the median survival time in relatively low risk group was significantly longer than that in relatively high risk group [27(20.3,33.7) months vs 9(5.9,12.1) months] (P<0.05). The survival time of MDS patients with different risks displayed the trend of shorting feature along with increasing of methylated genes (P<0.05).

CONCLUSIONThe combined detection of above menthioned 4 genes can improve the accuracy of early diagnosis and prognosis evaluation for MDS patients.

OBJECTIVETo analyze the methylation status of p15, DAPK, SOCS1 and FHIT genes in patients with myelodysplastic syndrome(MDS) and to explore the prognostic significance of gene methylation.

METHODSMethylation-specific PCR (MSP) was used to detect the methylation of the above-mentioned 4 genes in 67 patients with MDS and 18 patients with iron-deficient anemia as controls. The gene methylation status of MDS patients and its effect on prognosis were analyzed.

RESULTSThe methylation rates of p15, DAPK, SOCS1 and FHIT in 67 MDS patients were 37.3%, 35.8%, 47.8% and 52.2%, respectively, which were significantly higher than those in the control group (P<0.05). The methylation status of p15, SOCS1 was increased along with the increase of International Prognostic Scoring System(IPSS) scores (P<0.05), and ≥2 genes was more frequent in relatively high risk groups (P<0.05). The median overall survival time of patients with and without methylation were 15 and 21 months, respectively (P<0.05). Patients showing methylation of SOCS1 had a significantly shorter survival time in relatively low risk groups(P<0.05), meanwhile SOCS1, p15 and methylations of ≥2 genes had significantly shorter survival time in relatively high risk groups(P<0.05). In multivariate analysis, SOCS1 and p15 were negative prognostic factors.

CONCLUSIONp15, DAPK, SOCS1 and FHIT are higher hypermethylated genes in MDS. The methylations of SOCS1 and p15 are independent prognostic factor for overall survival in MDS.

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 expression level and clinical significance of Gli1 gene in patients with myelodysplastic syndrome(MDS). METHODS: The positive rate of bone marrow CD34 cells was detected by flow cytometry in 53 patients with MDS.Magnetic beads were used to separate CD34 cells. The expression of Gli1 on CD34 cells was detected by RT-qPCR, 25 patients with iron deficiency anemia were selected as controls. The relationship of Gli1 expression with clinical characteristics were analyzed. RESULTS: The expression of Gli1 in patients with MDS (0.73±1.26) was significantly higher than that in the control group (0.07±0.46) (P＜0.05). The expression of Gli1 significantly correlated with platelet count, chromosome grouping and IPSS risk stratification (P＜0.05). The median overall survival time of patients in high and low expression groups were 7 and 20 months respectively (P＜0.05). Multivariate analysis showed that Gli1 and chromosome grouping were 2 independent poor prognostic factors (P＜0.05). CONCLUSION The expression of Gli1 is high in MDS. Abnormal expression of Gli1 positively correlates with clinical characteristics and prognosis of patients.Gli1 may be involved in the occurrence and development of MDS.
Bone Marrow Cells ; Flow Cytometry ; Humans ; Myelodysplastic Syndromes ; Prognosis ; Zinc Finger Protein GLI1

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