No abstract available.
Azacitidine ; Decitabine ; Leukemia, Myeloid, Acute ; Salvage Therapy ; Myelodysplastic Syndromes

OBJECTIVE: To investigate the effect of decitabine on proliferation and apoptosis of multiple myeloma KMS-18 cells and its possible mechanism. METHODS: CCK-8 was used to detect cell proliferation, flow cytometry was used to detect the changes of apoptosis, real-time quantitative PCR was used to detect the expression of P53 gene mRNA in myeloma KMS-18 cells, and MSP assay was used to detect the methylation status of P53 gene promoter. RESULTS: The proliferation inhibition and apoptosis of KMS-18 cells significantly increased after treatment by decitabine (P＜0.05). The expression of P53 mRNA increased in KMS-18 cells after treatment of decitabine (P＜0.05). The methylation status of the P53 gene promoter in KMS-18 cells could be partially reversed by decitabine. CONCLUSION Decitabine can inhibit the proliferation of KMS-18 cells and induce their apoptosis, its mechanism ralates with partially reversing the methylation of P53 gene promoter in KMS-18 cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; DNA Methylation ; Decitabine ; Humans

OBJECTIVE: To study therapeutic efficacy and side effects of single decitabine for DNMT3A myelodysplastic syndrome (MDS) patients. METHODS: The clinical characteristics, efficacy and side effects of 59 myelodysplastic syndrome patients received the decitabine therapy in our center from January 2015 to December 2018 were retrospectively analyzed. Based on gene mutations, these patients were divided into 2 groups: DNMT3A MDS patients (n=27) and DNMT3A MDS patients (n=32). All patients in two groups were treated with decitabine for 4 circles. The efficacy and side effects in the two groups were compared. RESULTS: The median age of patients in DNMT3A MDS group was 56.2 (37-81) which was no statistic difference from DNMT3A MDS group. And there was no statistical difference including age, white blood cells, hemoglobin and platelet count between the two groups (P＞0.05). The ORR and complete response (CR) rate of DNMT3A group were 70.37% and 40.74%, the ORR and CR rate of DNMT3A group were 40.63% and 21.88% respectively. Significant differences were observed in ORR rate (P=0.035) between two groups. However, significant differences did not found in CR rate (P=0.159) between two groups, The similar adverse reaction was observed in DNMT3A and DNMT3A MDS patients. Among the 59 patients, 21 patients showed TP53+ mutation. DNMT3A/TP53 MDS patients (n=13) had similar ORR and CR compared with the DNMT3A/TP53 MDS patients (n=8) (P＞0.05). The overall survival (OS) in DNMT3A MDS group and DNMT3A MDS group were 29.1±13.4 months and 27.8±14.4 months, respectively, no significant differences between two groups were observed (P=0.475). CONCLUSION Decitabine treatment is an effective and safe for DNMT3A MDS patients, but not shows better survival advantage.
Azacitidine ; Decitabine ; Humans ; Myelodysplastic Syndromes ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo investigate the effect of all transretinoicacid(ATRA) combined with decitabine (5-Aza-2'-deoxycytidine;DAC) on DNA methylation and gene expression of p16INK4a (p16) and retinoic acid receptor β (RARβ), and to explore their combined anti neoplastic effect on U937 cells and newly diagnose delder acute myeloid leukemia(AML) patients.

METHODSThe expression levels of p16 and RARβ were determined by qRT-PCR and Western blot. Methylation-specific PCR was used to analyze their methylation status. WST-1 and flow cytometry were performed to detect growth inhibition, differentiation, apoptosis and cell cycle of U937 cells respectively.

RESULTSThe expression p16 and RARβ was down-regulated by promoter hypermethylation in newly diagnose delder AML patients and U937 cells. Combination treatment of ATRA and DAC induced DNA hypomethylation as well as gene expression of p16 and RARβ, which contributed to the growth inhibition, differentiation, apoptosis and cell cycle arrest of U937 cells. In addition for elder AML patients intolerable to standard chemotherapy, the combination regimen of ATRA and DAC showed antineoplastic activity accompamied by up-regulation of p16 and RARβ expression and decrease of bone marrow blast, moreover the parients showed good tolerence to the reginen.

CONCLUSIONThe regimen of ATRA combined with DAC as the combination therapeutic strategy for inducing differentiation and demethylation possesses the anti-AML potency, and contributes to optimizing the therapeutic strategy for elder AML patients and promoting the clinical prognosis.

OBJECTIVE: To investigate a reliable clinical indication for predicting the therapeutic response of decitabine therapy in the patients with myelodysplastic syndromes (MDS). METHODS: The clinical efficacy of decitabine for 55 cases of MDS was analyzed retrospectively. According to the lymphocyte level at d28 after the first time treatment with decitabine, the patients were divided into high lymphocyte level group (H-Lym≥1.2×10/L) and low lymphocyte level group (L-Lym<1.2×10/L), and the overall response rate (ORR) and the progression-free survival (PFS) time in 2 groups were compared. RESULTS: As compared with L-Lym group, the ORR and PFS time in H-Lym group were significantly enhanced ［(76.0% vs 50.0%) (P<0.05) and median time (15.7 months vs 8.5 months)(P<0.05), respectively］;the ratio of platelet level ≥100×10/L in H-Lym group was very significantly higher than that in L-Lym group (72.0% vs 20.0%)(P<0.01). Multivariat analysis showed that the risk of disease progression in L-Lym group was 4.45-fold of H-Lym group (95% CI:1.58-12.59)(P<0.05). CONCLUSION The patients with lymphocyte level ≥1.2×10/L at day 28 after the first time treatment with decitabine show the higher ORR and longer PFS time, therefore. the lymphocyte level at day 28 after first time treatment with decitabine can be used as an early clinical indicator for predecting the response to decitabine treatment.
Antimetabolites, Antineoplastic ; Decitabine ; Humans ; Lymphocytes ; Myelodysplastic Syndromes ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To explore the clinical efficacy of decitabine for treatment of patients with myelodysplastic syndrome (MDS) and factors predicting the prognosis. METHODS: The clinical data of 87 patients with MDS treated with decitabine were analyzed retrospectively. The hENT1 mRNA expression and TP53 gene mutation were detected by Q-PCR and gene target sequencing, respectively. The relationship of clinical characteristics and molecular indicators with the clinical response to decitabine was analyzed. RESULTS: In treatment for median 4 (2-17) courses, a total 51 patients (58.6%) showed therapeutic responses, including CR in 17 cases, PR in 12 cases, mCR in 9 cases, HI in 13 cases; 36 (41.4%) patients showed non-response. Univariate analysis showed that the patients with the complex karyotype, monosomal karyotype, chomosome 7 abnormality and Plt count doubling after 1 course treatment had a high CR rate, while the patients with relative high risk by IPSS (intermediate risk 2+ high risk), complex karyotype and Plt count doubling after 1 course had much more high overall remission rate (ORR). The expression level of hENT1 mRNA in MDS patients with response was significantly higher than that in patients without response ［(1.78±1.45 (2) vs 0.96±0.97 (2)(P= 0.002)］. Among 51 patients with therapeutic response, the expression level of hENT1 mRNA in CR group was higher than that in non-CR group ［(2.58±1.44 (2) vs 1.39 ±1.3 (2), P= 0.005)］. Among 52 patients in relative high risk (intermediate risk 2 +high risk), the median OS time of patients with high hENT1 mRNA expression was significantly longer than that of patients with low hENT1 mRNA expression (31 vs 12 months)(P<0.001). Among 87 patients received decitabine treatment, the TP53 gene mutation occured in 11 (12.6%) patients. The ORR in patients with TP53 mutation was high (P=0.04), moreover the patients with TP53 mutation more easily gained CR (P<0.001). Multivariate logistic regression model showed that the complex karyotype, Plt count doubling after 1 course treatment, TP53 mulation and high expression of hENT1 mRNA were the independent prognostic factors for predicting the CR after decitabine treatment. CONCLUSION IPSS staging, complex karyotype, Plt count doubling after 1 course treatment and hENT1 mRNA expression, TP53 gene mutation can be used to predict the tharapeutic efficacy of dectitabine for treatment of MDS.
Decitabine ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Prognosis ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the clinical features of acute myeloid leukemia patients aged over 80 years. METHODS: The clinical data from 24 cases of acute myeloid leukemia (non-M3) aged over 80 years were analyzed retrospectively. Clinical characteristics, therapeutic efficacy and overall survival rate of the patients received low dose chemotherapy and/or decitabine were compared with that received only supportive care. RESULTS: According to FAB classification, the 10 patients were M2 subtypes (41.7%), the 7 patients were M4 subtypes (29.2%), the 4 patiens were M5 (16.7%), the 3 patients were unclassifed (16.5%). 22 patients (91.0%) were complicated with underling diseases. Among 13 patients received low dose chemotherapy or decitabine, 8 cases (61.5%) achived partial remission or higher remission. The median survival time of patients who reseived chemotherapy was 30 weeks, and signicantly longer than that of patients received supportive care (median survival time was 9 weeks (P<0.05)). The univariated analysis showed that WBC≥50×10/L, ECOG≥2 and received supportive care were unfavonrable prognostic factors for overall survival. CONCLUSION More than half of patients aged over 80 years who received individudized treatment can achieve partial remission or higher remission, and can have more longer survival time..
Aged, 80 and over ; Decitabine ; Humans ; Leukemia, Myeloid, Acute ; Retrospective Studies ; Survival Rate ; Treatment Outcome

OBJECTIVE: To investigate the clinical efficacy and safety of low-dose decitabine (DAC) alone for treatment of myelodysplastic syndrome (MDS) Methods: Fifty-one patients with meddle- and high-risk MDS were selected, and were randomly divided into A, B and C groups according to the drug regimens: the therapeutic regimen in A group consisted of low dose DAC 10 mg/(m·d)×7 d; the therapeutic regimen in B group: normal dose DAC 20 mg/(m·d) ×5 d; the therapeutic regimen in C group: low dose DAC+CAG DAC 10 mg/(m·d) d 1-5，cytarabine 10 mg/(m·d) q12h d 1-7, aclaromycin 10 mg/d d 1-4，G-CSF 200 μg/(m·d), d 1-7. All patients in 3 groups were treated for 4 circles. The efficacy and response were compared among 3 groups. RESULTS: The complete remission rates (CR%) in A, B and C groups were 18.75%, 22.22% and 23.53% respectively, and the overall response rate (ORR%) in A, B and C groups were 56.25%, 61.11% and 58.82% respectively, without statistical difference among 3 groups (P＞0.05)．After 1 year of follow-up, the survival rate was not significantly different among 3 groups, the blood cell accounts were higher than the basic value. After 1 course of treatment, the inhibition rate of III-IV grade myelosuppression was statistically significantly different among the 3 groups (P＜0.05), and the infection rate among 3 groups also was statistically different, The incidence of myelosuppression and infection in A group was significantly lower than that in B and C groups. The per capita blood transfusion during the four-month treatment was not statistically different among 3 groups. however, that in the A group was lesser than B and C groups. CONCLUSION The therapeutic efficacy of low dose decitabine alone for treatment of MDS is equal to routine dose decitabine and decitabine plus CAG, but the low dose group shows less myelosuppressive and more safe effects.
Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Decitabine ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Treatment Outcome

OBJECTIVE: To investigate the effects of decitabine combined with bortezomib on the proliferation of mantle cell lymphoma cell lines (Jeko-1 and Grante519) in vitro and explore the underlying mechanisms. METHODS: Jeko-1 and Grante519 cells were treated with different concentrations of decitabine and/or bortezomib alone and their combination.The cell proliferation was determined by CCK-8 assay. the cell apoptosis were detected by flow cytometry, the mRNA and protein expression levels of genes related with the cell cycle and apoptosis were analyzed by RT-PCR and Western blot respactively. RESULTS: Low dose DAC could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner. After DAC treatment, caspase 3, BAX and PCDH8 expression levels increased, while BCL-2 and CCND1 expression levels decreased in Jeko-1 and Grante519 cells, but there was no significant difference in NF-κB expression. High dose BTZ could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner; single drug BTZ could increase the expression level of Caspase 3 and BAX, and decrease the expression level of NF-κB, BCL-2 and CCDN1 in Jeko-1 and Grante519 cells, but there was significant difference in PCDH8 expression level. Compared with single-drug treatment group, DAC combined with BTZ significantly increased the inhibitory rate and apoptotic rate of Jeko-1 and Grante519 cells; PCDH8, Caspase 3 and BAX expression levels significantly increased, and the expression levels of NF-κB, BCL-2 and CCND1 significantly decreased in Jeko-1 and Grante519 cells. CONCLUSION The combination of DAC and BTZ has obviously synergistic effects on the growth inhibition of Jeko-1 and Grante519 cells which maybe relates with enhancing inbibitory effect on NF-κB signal pathway, down-regulating BAX expression, up-regulating BAX expression as well as increasing cospase 3 expression. This study provides a novel therapeutic approach for mantle cell lymphoma.
Adult ; Apoptosis ; Bortezomib ; Cadherins ; Cell Line, Tumor ; Cell Proliferation ; Decitabine ; Humans ; Lymphoma, Mantle-Cell

OBJECTIVE: To analyze the relationship between the promoter methylation status of Tripartite-motif protein 58 (TRIM58) and its mRNA expression level in acute myeloid leukemia (AML), and to explore the expression and regulation of TRIM58 in AML. METHODS: The bisulfite sequencing PCR (BSP) and quantitative real-time PCR (qPCR) technologies were used to detect the promoter methylation status and expression levels of TRIM58 mRNA in primary CD34⁺ and CD34^- AML cells and the AML cell lines KG1a and K562 were determined. RESULTS: The expression of TRIM58 mRNA in CD34⁺ cells was down-regulated in 10 AML patients, while that in CD34^- cells was down-regulated in 12 cases. Differences in the promoter methylation level of TRIM58 were statistically significant between AML group and normal control group (P<0.05). Additionally, the expression of TRIM58 mRNA was down-regulated in cell lines KG1a and K562, and up-regulated after decitabine treatment. CONCLUSION The down-regulation of mRNA expression of TRIM58 in AML cells may be related to its promoter methylation status.
DNA Methylation ; Decitabine ; Humans ; Leukemia, Myeloid, Acute/metabolism* ; RNA, Messenger/metabolism* ; Tripartite Motif Proteins/metabolism*