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In the treatment of Hodgkin lymphoma (HL), it is important to avoid delayed side effects while improving efficacy, the immunotherapy provides an excellent option. The programmed death receptor 1 (PD-1) inhibitors are effective drugs for the treatment of relapsed/refractory HL. Meanwhile, the high effectiveness and tolerance of PD-1 inhibitors also provide the possibility for combination therapy. This article reviews the research progress of PD-1 inhibitors in the treatment of relapsed/refractory HL.
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Objective:To evaluate the efficacy and safety of modified FC/ATG pretreatment in the treatment of severe aplastic anemia(SAA).Methods:From June 2012 to June 2020, clinical data of 64 patients with severe aplastic anemia undergoing allogeneic hematopoietic stem cell transplantation with modified FC/ATG(Flu 30 mg·m -2·d -l, -5~-2 d、CTX 50 mg·kg -1·d -1~-2 d、ATG: 2.5 mg·kg -1·d -1, -5~-2 d) pretreatment were retrospectively analyzed.There were MSD-HSCT ( n=29) and Haplo-HSCT ( n=35). Results:One patient died of intracerebral hemorrhage before transplantation and the remainders were completely implanted.During a median follow-up period of 14.5(1-95) months, overall survival (OS) rate of 92.2%.It was significantly higher than OS rate of 67.2% in the treatment of SAA by foreign pretreatment regimens containing low-dose TBI.And pretreatment scheme containing FC+ BU/TBI had an OS of slightly >91.3% in the treatment of SAA.The 3-year OS rates were 85.7% and 93.5% in Haplo-HSCT and MSD-HSCT groups ( P=0.058). The OS rate of SAA Haplo-HSCT/MSD-HSCT group was similar to that of " Beijing Protocol" (BU/CY+ ATG) (89%, 91%). The viral infection rates of EB and CMV were significantly higher in haplo-HSCT group than those in MSD-HSCT group and inter-group difference was statistically significant ( P<0.05). However, univariate analysis showed that two groups had no effect on survival time ( P=0.403, P=0.132). Univariate analysis showed that survival time was significantly associated with the presence of Ⅲ-Ⅳ° aGVHD and the presence of severe complications ( P=0.007, P=0.001). Further multivariate analysis revealed that severe complication was an independent risk factor for survival ( P=0.003). Conclusions:The efficacy of improved FC/ATG pretreatment in the treatment of SAA in MSD-HSCT or Haplo-HSCT is higher than other domestic and international pretreatment schemes in OS rate, safety and effectiveness.Onset of severe complication and association with Ⅲ ~ Ⅳ ° aGVHD are the influencing factors for patient survival.The efficacy of Haplo-HSCT group is similar to that of MSD-HSCT group.It may be employed as an alternative donor for SAA patients without fully congruent donors.
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Objective:To compare the effects of two pretreatment schemes on the efficacy, gonad and reproductive function of haploid hematopoietic stem cell transplantation recipients with severe aplastic anemia(SAA).Methods:The data of 73 patients with SAA who underwent haploid hematopoietic stem cell transplantation were analyzed retrospectively.The pretreatment scheme was divided into Fludarabine+ Cyclophosphamide+ Antithymocyte globulin group(FC lowATG group, 45 cases)and Busulfan+ Cyclophosphamide+ Antithymocyte globulin group(Bucy/ATG group, 28 cases). The changes of blood cell implantation time, follicle stimulating hormone(FSH), luteinizing hormone (LH), estradiol and testosterone were compared between the two groups. Results:there was no significant difference in blood cell implantation time between the two groups( P=0.096; P=0.133). The levels of FSH and LH in female recipients in Bucy/ATG group were higher than those in FC lowATG group, and the level of estradiol was lower than that in FC lowATG group.There were significant differences between the groups(all P<0.05). The pregnancy or fertility rate of female recipients in Bucy/ATG group was lower than that in FC lowATG group(all P<0.05). There was no significant difference in FSH, LH, testosterone and fertility between the two groups(all P>0.05). There was no significant difference in 2-year overall survival rate and failure free survival rate between the two groups( P=0.091; P=0.084). Conclusions:FC lowATG may be an effective pretreatment scheme for haploid hematopoietic stem cell transplantation in SAA with less damage to gonad and reproductive function.
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Objective:To investigate the effects of histone deacetylase inhibitor Chidamide (CS055) and DNA methyltransferase inhibitor decitabine (DAC) on proliferation and apoptosis of acute myeloid leukemia cell line U937 and its possible mechanism.Methods:U937 cells were cultured in vitro and treated with CS055 (CS055 single drug group), DAC (DAC single drug group), combination (combined drug group)and a negative control group. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the proliferation inhibition rate. The apoptosis rate was detected by flow cytometry.The mRNA expression of DNA methyltransferase 1 (DNMT1) was analyzed by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Western blot was used to analyze the expression of acetylated histone H3 and DNMT1. Results:The proliferation inhibition rate of U937 cells treated with CS055 and DAC increased significantly in a time-dose-dependent manner. The inhibitory effect of the combination group was more obvious than that of the single drug group. Flow cytometry showed that the 72 h apoptotic rates in the control group, 0.25 μ mol/L CS055 group and 2.5 μ mol/L DAC group were (0.67±0.12)%, (23.43±0.50)%, (8.47±0.32)%, (32.73±0.42)%. The apoptotic rate was significantly increased in the combination group compared with the single drug group. qRT-PCR showed that the expression of DNMT1 mRNA was down-regulated after CS055 and DAC treat alone; the down-regulating effect of the combination group was more significant. Western blot showed that the up-regulation of Ac-H3 and the decrease of DNMT1 in the combination group were significantly higher than those in the single drug group.Conclusions:The application of CS055 and DAC alone could inhibit the proliferation and induce apoptosis of U937 cells. The combination of the two drugs has obvious synergistic effect. The mechanism is that histone deacetylase inhibitors have demethylation effects, and demethylation drugs also have the effect of histone deacetylase inhibitors, which in combination increases demethylation and increases histone deacetylation.
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Objective:To explore the effects and mechanisms of bortezomib on the proliferation and apoptosis of acute T lymphocyte leukemia cell line Jurkat.Methods:MTT assay was used to test the influence of bortezomib on the proliferation of Jurkat cells.Flow cytometry was used to detect the influence of bortezomib on apoptosis of Jurkat cells.Real-time quantitative polymerase reaction(RT-PCR) was used to detect the effects of bortezomib on the expression of Bax, Bcl-2 and Cox-2 genes in Jurkat cells.Results:The inhibition rates of 5ng/mL, 10ng/mL, 20ng/mL and 40ng/mL bortezomib on Jurkat cells at 24h were (13.23±0.71)%, (39.53±0.95)%, (53.07±1.12)%, (60.43±0.75)%, respectively, and the inhibition rates at 48h were (25.20±0.96)%, (52.80±1.30)%, (60.67±0.64)%, (75.10±1.35)%, respectively.The inhibitory rates of proliferation of Jurkat cells at 72h were (38.37±0.93)%, (60.94±0.85)%, (73.83±5.08)%, (88.37±1.55)%, respectively.The inhibitory rates of proliferation of Jurkat cells increased with the increase of drug concentration and the prolongation of action time, and the differences were statistically significant( F=1 602.202, 1 085.089, 181.034, all P<0.05). Bortezomib (5ng/mL, 10ng/mL, 20ng/mL and 40ng/mL) treatment for 24h, 48h and 72h, the apoptosis rate of Jurkat cells increased with the increase of drug concentration and the prolongation of action time, the differences were statistically significant( F=1 288.571, 223.378, 251.175, all P<0.05). The expression of Bax mRNA in Jurkat cells increased with the increase of drug concentration and time( F=258.446, 518.929, 276.764, all P<0.05). The Bcl-2 mRNA and Cox-2 mRNA expression levels decreased with the increase of drug concentration and the prolongation of action time( FBcl-2 mRNA=236.848, 264.849, 343.968, FCox-2 mRNA=679.404, 1288.681, 1541.850, all P<0.05). Conclusion:Bortezomib can inhibit the proliferation and induce apoptosis of Jurkat cells.Bortezomib can increase the expression of Bax mRNA and decrease the expression of Bcl-2 and Cox-2 mRNA, which may be the molecular mechanism of bortezomib to promote apoptosis.
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Objective:To explore the characteristics of gene mutations in patients with myelodysplastic syndromes (MDS) and the values of these mutations in prognosis assessment and curative effect prediction.Methods:The clinical data of 110 patients with newly diagnosed MDS who were admitted to Shanxi Bethune Hospital from January 2017 to December 2019 were retrospectively analyzed. The next-generation sequencing technology was used to detect mutations of 45 MDS-related genes. The patients' clinical features, results of laboratory tests, revised International Prognostic Points System (IPSS-R) scores and therapeutic responses to decitabine were analyzed and compared between the gene mutation and non-mutation groups.Results:Among 110 patients with MDS, 83.6% (92/110) of patients harbored at least one mutation. Thirty-eight gene mutations were detected, and the mutation rates of the most common mutations of ASXL1, TET2, TP53, and SF3B1 were 19.1% (21/110), 17.3% (19/110), 15.5% (17/110), and 12.7% (14/110). The IPSS-R scores of MDS patients with more mutations were higher ( F = 44.493, P < 0.01). The IPSS-R score of the SF3B1 mutation group was lower than that of the SF3B1 non-mutation group [(3.50±1.52) points vs. (4.76±1.58) points, t = -2.802, P = 0.006], and the IPSS-R score of the U2AF1 mutation group was higher than that of the U2AF1 non-mutation group [(5.78±1.39) points vs. (4.50±1.60) points, t = 2.320, P = 0.022], and the IPSS-R score of the TP53 mutation group was higher than that of the TP53 non-mutation group [(5.71± 2.24) points vs. (4.40±1.41) points, t = 2.329, P = 0.031]. There was no significant difference in IPSS-R scores between patients with and without other mutations (all P > 0.05). The overall response rate to decitabine in the TP53 mutation group was higher than that in the TP53 non-mutation group [83.3% (10/12) vs. 43.1% (22/51), χ2 = 6.280, P = 0.012], and the TP53 mutation group had a higher complete remission rate [50.0% (6/12) vs. 19.6% (10/51), χ2 = 4.736, P = 0.030]. Conclusions:Genetic mutations are common in MDS patients. Patients with SF3B1 mutation have a good prognosis, while those with U2AF1 and TP53 mutations have a poor prognosis, and patients with TP53 mutation have a high response rate to decitabine.
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Objective@#To compare the clinical efficacy and safety of bortezomib, cyclophosphamide, dexamethasone (VCD) regimen and bortezomib dexamethasone (VD) regimen in the treatment of the patients with newly diagnosed multiple myeloma (NDMM).@*Methods@#The clinical data of 73 patients with NDMM in Shanxi Dayi Hospital from January 2013 to January 2016 were retrospectively analyzed. According to the chemotherapy regimen, the patients were divided into VCD group (41 cases) and VD group (32 cases). The efficacy and adverse reactions of the two groups were evaluated.@*Results@#The overall response rate of VCD group and VD group was 80.5% (33/41) and 78.1% (25/32) respectively, and the difference was not statistically significant (χ 2= 0.061, P= 0.804); and complete remission (CR) rate was 36.6% (15/41) and 15.6% (5/32) respectively, and the difference was statistically significant (χ 2= 3.970, P= 0.046); the median progression-free survival (PFS) was 27 months and 24 months respectively, and the median overall survival (OS) was 35 months and 33 months respectively, and the differences were not statistically significant (all P > 0.05). Most adverse reactions occurred in grade 1-2, in which peripheral polyneuropathy and thrombocytopenia were the most common. Peripheral neuritis was the most common finding among the adverse reactions of grade 3. The incidence of adverse reactions in both groups was not statistically significant (P > 0.05).@*Conclusions@#VCD and VD regimen could be recommended as a better induction therapy for NDMM patients. Compared with VD scheme, VCD scheme has a higher CR rate.
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Richter syndrome (RS) is a rare disease of the lymphohematopoietic system. It is defined as the transformation of a low-grade malignant lymphoproliferative disorder into a more aggressive lymphoproliferative disorder, most commonly, diffuse large B-cell lymphoma (DLBCL). The disease is rare in the clinic and has nonspecific clinical manifestations. An excisional lymph node biopsy is considered the gold standard for diagnosis of RS; 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) can help inform the optimal site for biopsy. The main treatment strategies are chemotherapy, hematopoietic stem cell transplantation (HSCT), participating in a clinical trial of a new medicine, and others, but the overall prognosis is poor. At present, there is no sufficient treatment for the disease. In order to improve the awareness of disease and identify it among a variety of similar diseases, while aiming to discuss treatment strategies, this article reviewed RS in terms of the risk factors, clinical manifestations, diagnosis, treatment, and prognosis.
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Objective To study the suppressive mechanism of the bromo structural domain inhibitor JQ1 on the acute myeloid leukemia cell line U937 and its regulation of the STAT-5 signaling pathway. Methods U937 cells in the logarithmic growth phase were tested. Each experimental group was fed with 0.2, 1.0 and 4.0μmol/L of JQ1, and a blank control group without JQ1 was set up. U937 cells were cultured for 48 h, and the cell proliferation inhibitory rate was measured by MTT assay. Flow cytometry (FCM) was used to detect the apoptotic rate. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of focal adhesion kinase (FAK) and P21 activated kinase (PAK1). The expression of STAT-5 protein was analyzed by Western blot. Results Different concentration of JQ1 could inhibit the proliferation of U937 cells in a time and dose-dependent manner, and different concentration of JQ1 could induce the apoptosis of U937 cells in a dose-dependent manner. Treatment of U937 cells with different concentrations of JQ1 (0.2, 1.0 and 4.0 μmol/L) reduced the expression of FKA mRNA and PAK1 mRNA after 48 h, the expression of FAK mRNA was 0.417±0.066, 0.140±0.026, and 0.027±0.006 (F=454.651, P=0.000), and the expression of PAK1 mRNA was 0.533±0.045, 0.080±0.010, and 0.010±0.001 (F=2434.610, P= 0.000), and STAT-5 protein expression was also significantly inhibited. The expression of STAT-5 protein in U937 cells after treated with different concentrations of JQ1 (0.2, 1.0 and 4.0 μmol/L) for 48 h were 0.71± 0.19, 0.62±0.16, 0.53±0.14, and 1.00±0.21 in the control group (F= 263.135, P= 0.000). Conclusion JQ1 can effectively inhibit the proliferation of the acute myeloid leukemia cell line U937 cells and induce their apoptosis, and the possible mechanism of action is regulated via STAT-5 signaling pathway.
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Objective@#To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m2, 10 mg/m2 or 12 mg/m2 as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) .@*Methods@#A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m2) as induction chemotherapy in newly diagnosed patients of adult AML.@*Results@#Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m2 group and IDA 12 mg/m2 group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m2 group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m2 was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m2 when compared with the IDA 8 mg/m2 was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×109/L in IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×109/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) .@*Conclusions@#For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m2 is clinically superior to IDA 8 mg/m2 and IDA 12 mg/m2 in favorable intermediate AML subgroup. However, idarubicin 12 mg/m2 is more suitable to adverse AML subgroup.
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The incidence of elderly patients with acute myeloid leukemia (AML) is increased year by year, and the median onset age is 67 years old. As old patients often have the viscera dysfunction, it is still lack of unified treatment clinically. This article summarizes the latest research progress of elderly patients with AML in the 58th American Society of Hematology Annual Meeting.
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Objective To explore the effect of proliferation and apoptosis,and research its mechanism associated with RAS/extracellular signal regulated kinase/mitogen-activated protein kinase (RAS/ ERK/MAPK) in Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation acute lymphocytic leukemia cell line MV4-11 cells treated by triptolide (TP).Methods MV4-11 cells were respectively treated by triptolide with diverse concentrations and different times.The proliferation inhibition rate was measured by methyl thiazolyl tetrazolium,the apoptosis rate was detected by flow cytometry,the mRNA expressions of FLT3,RAS,ERK,forkhead box protein M1 (FOXM1),and c-Myc were analyzed by realtime fluorescent quantitative polymerase chain reaction (PCR).Results The proliferation inhibition rate markedly increased in a dose-time dependent manner after MV4-11 cells were treated by TP.After cells were treated with 10,and 20 nmol/L TP,respectively,the apoptosis rates at 48 h were (17.30 ± 0.56) ％,(35.77 ±0.55)％,and those at 72 h were (49.83 ±0.45)％,(68.90 ±0.75)％ correspondingly.PCR data showed that the mRNA level of FLT3 mRNA decreased obviously,and that of RAS,ERK,FOXM1,and c-Myc also decreased.Conclusions Triptolide could significantly inhibit the MV4-11 cells proliferation and induce cell apoptosis,and its mechanism might be through inhibiting the expression of related genes on RAS/ERK/MAPK signaling pathway.
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Objective To investigate the effects of triptolide (TP) on proliferation and apoptosis of acute myeloid leukemia cell line MV411 with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), and its effect on PI3K-Akt-mTOR pathway. Methods MTT assay was used to detect the proliferation inhibition of MV411 cell proliferation treated by different concentrations of TP in 24, 48 and 72 h. Flow cytometry was used to measure the cell apoptosis rate at 48 and 72 h. Real-time fluorescent quantitative PCR was used to detect the expression of FLT3, PTEN, PI3K, Akt, mTOR mRNA on PI3K-Akt-mTOR pathway. Results After treated by 0, 5, 10, 20, 40, and 80 nmol/L TP in 24, 48 and 72 h, the viability of MV411 cells was inhibited in a time-dose dependence manner. MV411 cells was treated by 0, 10, and 20 nmol/L TP after 48 and 72 h, the cell apoptosis rates were rising with the increasing of drug concentration, there were statistical significances [48 h:(3.30±0.20) %, (17.10±0.36) %, (35.67±0.61) %, 72 h: (7.37±0.32) %, (49.33± 0.40)%, (68.92±0.11)%, all P=0.000]. The expressions of FLT3, PI3K, Akt, and mTOR mRNA were down-regulated and PTEN mRNA expression was up-regulated by TP. Conclusion TP may inhibit the proliferation and induce apoptosis of MV411 cells by affecting the expression of PI3K-Akt-mTOR pathway related genes.
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Objective To observe the clinical effects and safety of sodium valproate combined with decitabine for treatment of myelodysplastic syndrome (MDS). Methods Forty-two patients with MDS were enrolled in department of hematology in Shanxi Dayi Hospital from February 2012 to February 2017. According to random number table, the patients were divided into the control group (21 cases) and the experimental group (21 cases). The patients in the control group received decitabine at the dose of 20 mg·m-2·d-1, and intravenous infusion was completed in 2 hours, continuous therapy up to 5 days, 4 weeks as a course; the patients in the experimental group received combined medication, orally given sodium valproate 0.2 g once, 3 times per day. One week later, the dosage was added to 0.4 g once, 3 times per day. Both groups received at least 4 courses of treatment. The treatment was stopped when serious adverse reactions or obvious disease progression occurred. The bone marrow smear was rechecked every 4 weeks after treatment to evaluate the efficacy. The expressions of ASXL1, DNMT3A and TET2 in bone marrow cells were detected by fluorescence quantitative PCR before and after treatment. Results The total treatment response rate of the experimental group and the control group were 76.2 % (16/21) and 57.1 % (12/21) respectively, and there was statistically significant difference (P< 0.05); the total remission rate of the two groups was 47.6 % (10/21) and 38.1 %(8/21) respectively, and there was no significant difference (P> 0.05). All patients had slight adverse reactions, and the adverse reaction rate was 42.9 % (9/21) and 38.1 % (8/21), and there was no significant difference (P>0.05). The content of TET2 mRNA and DNMT3A mRNA after treatment in both groups were decreased compared with the expressions before treatment, and there were significant differences (P<0.05). However, there was no significant difference between the two groups after treatment (P> 0.05); the content of ASXL1 mRNA had no obvious change in the control group and a dramatic decrease in the experimental group compared with that before treatment (P<0.05). Conclusion Sodium valproate combined with decitabine has favorable effects and mild adverse reactions for treatment of MDS, besides, it can influence the expressions of TET2, DNMT3A and ASXL1.
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Objective To explore the apoptosis of K562/G01 cells induced by triptolide through MDM2/p53 signaling pathway. Methods K562/G01 cell line was treated with different concentrations of triptolide. MTT was used to detect the cell proliferation inhibition rate. FCM was used to determine the apoptosis rate changes in 12 h and 24 h. The mRNA expression levels of bcr-abl, XIAP, MDM2, p53 were detected by real-time quantitative PCR. Results After treatment by 10, 20, 40, 80, 100 nmol/L TP in 12, 24, 48 h, the viability of K562/G01 cells was inhibited in time-dose dependence manner. K562/G01 cells was treated by 20 nmol/L, 40 nmol/L TP after 12 h, 24 h, the cell apoptosis rate was rising with drug concentration and time. The bcr-abl, XIAP, MDM2 mRNA expression was down-regulated and p53 mRNA expression was up-regulated by TP. Conclusion TP can inhibit the growth of K562/G01 cell line and induce apoptosis through XIAP-MDM2-p53 signaling pathway.
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Objective To investigate the impact of triptolide (TP) on proliferation and apoptosis of imatanib resistant CML cell (K562/G01) and its regulating effect on Wnt/β3-catenin signal pathway.Methods A series of 10,20,40,and 80 nmol/L of triptolide were used in CML cells K562/G01 for 12,24,and 48 hours.The cell proliferation was detected with methyl thiazolyl tetrazolium (MTT) test.The apoptosis was assessed with flow cytometry (FCM).The mRNA expressions of breakpoint cluster region-c-abl (BCR-ABL),β-catenin and its down-stream targets Lef-1,and cyclinD1 were analyzed with real-time quantitative polymerase chain reaction (RT-PCR),respectively.Results Triptolide significantly inhibited K562/G01 cell growth ability and induced apoptosis in a dose-dependent manner.Mter being treated with 20,40 nmol/L TP for 24 hours,the cell growth inhibition rates were (22.62 ± 1.33) ％,and (51.41 ±1.39) ％,respectively.The late apuptosis rates were (6.91 ± 0.14) ％,and (7.64 ± 0.47) ％,respectively.Meanwhile,PCR data showed that the mRNA levels of BCR-ABL were decreased,compared to the control group,the mRNA levels of β-catenin,Lef-1,and cyclinD1 were also decreased obviously after treatment.Conclusions Our data indicated that the triptolide could inhibit the proliferation and induce the apoptosis of K562/G01,and the mechanism might be related to the blockade of Wnt/β-catenin signal pathway.
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Objective To investigate the expression of DNA methyltransferase (DNMT) in HL-60 cells induced by tetrandrine (Tet).Methods HL-60 cells were treated with different concentrations of Tet and decitabine (DAC) alone and in combination with both.Methyl thiazolyl tetrazolium (MTT) assay was used to assess cytotoxic effect.Flow cytometry (FCM) was used to determine apoptosis rate.Real-time quantitative polymerase chain reaction (PCR) assay was used to quantify mRNA levels of DNMT.Western blot was used to quantify the expression of DNMT protein.Results Tet inhibited the growth and proliferation of HL-60 cells in a time-and dose-dependent manners (both P ＜0.01).Tet treated HL-60 cells after 48 h at the concentration of 2 μmol/L,and 4 μmol/L,the levels of DNMT gene and protein in the drug administration group decreased compared to the control group.After incubation for 48 h with Tet 2 μmol/L combined with DAC 4 μmol/L,the combination group was significantly depressed.Conclusions Tet could potently inhibit the growth and proliferation of HL-60 cells,reduce the expression levels of DNMT mRNA and protein,and have a more obvious effect in the combination group.
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Objective To observe the effect of bromodomain4 (brd4) inhibitor JQ1 on proliferation inhibition and apoptosis of Ph positive acute lymphocytic leukemia (Ph+ ALL) cells, and to explore the influence on the expression of brd4 and its downstream genes (myc and p53), and the reverse effect on bcr-abl.Methods Different concentrations of JQ1 were used on SUP-B15 cells.The proliferation inhibition rate was detected by MTT, the apoptosis rate was determined by flow cytometry (FCM), and the expressions of bcr-abl mRNA, brd4 mRNA, myc mRNA and p53 mRNA were detected by real-time fluorescent quantitative PCR (RT-PCR).Results Different concentrations of JQ1 inhibited SUP-B15 cells proliferation and induced cell apoptosis.The apoptosis rate was significantly increased compared with that in control group with a time-dose dependent manner.Median inhibitory concentration at 72 h was 1.0 pmol/L.At the same time, JQ1 decreased the transcription levels of bcr-abl mRNA, brd4 mRNA and myc mRNA, and increased the transcription level of p53 mRNA.Conclusions As a brd4 inhibitor, JQ1 can decrease the expression of brd4 to affect the expression of its downstream genes myc and p53, meanwhile, it can change the over expression of bcr-abl to suppress the proliferation of Ph+ ALL cells and induce apoptosis.
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Acute myeloid leukemia (AML) is a disease of the elderly.Treating acute myeloid leukemia in the elderly is the highlight in the 56th American Society of Hematology (ASH) annual meeting.The question of which elderly patients with AML benefit from conventional intensive chemotherapy versus hypomethylating therapy or novel agent remains uncertain.This article reviews the latest research presented at the 56th ASH annual meeting on the elderly AML.
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<p><b>OBJECTIVE</b>To study the effect of triptolide (TP) on the methylation status of human promyelocytic leukemia cells (HL-60) and explore a preliminary demethylation mechanism.</p><p><b>METHODS</b>Normal HL-60 cells as control group, the cell proliferation level of HL-60 cells was detected by MTT assay, being treated by different concentration TP (3.125, 6.25, 12.5, 25 nmol/L) for 24 h or 48 h respectively; Choosing the 3.125 nmol/L and the 6.25 nmol/L TP affected HL-60 cells for 48 h, the cell apoptosis rate and cell cycle were determined by flow cytometry, the expressions of death-associated protein kinase 1 (DAPK-1) and methyltransferase DNMT1, DNMT3B mRNA were measured by real time-PCR (RT-PCR), LINE-1, DAPK-1 genes'methylation variations were analyzed by methylation specific PCR (MSP).</p><p><b>RESULTS</b>Compared with control group, the different concentration TP could significantly inhibit the proliferation of HL-60 in a time-dose dependent manner (P<0.05, P<0.01). After being treated by TP for 48 h, the cell early apoptosis rate of control group and 6.250 nmol/L TP group were (2.07 ± 1.91)%, (9.77 ± 3.52)%, respectively (P<0.05); When the TP concentration increased, DAPK-1mRNA expression increased (P<0.01), DNMT1, DNMT3B mRNA expression significantly dampened (P<0.01); the promoter of LINE-1, DAPK-1 genes were hypermethylation state in the control group, after being treated by TP for 48 h, the brightness of LINE-1, DAPK-1 genes'methylation strips weakened, and the non-methylation strips enhanced all in a dose-dependent manner.</p><p><b>CONCLUSION</b>TP could down-regulate the transcriptional expression of methyltransferase DNMT1/3B genes, indirect action to reduce the degree of DAPK-1, LINE-1 genes mathylation, thus promote DAPK-1 gene expression level and inhibit the HL 60 cell growth.</p>