Objective Acute myeloid leukemia(AML)is a highly heterogeneous disease,and molecular events such as DNMT3A gene mutations are associated with poor prognosis in AML patients.Consequently,there is an urgent need for a n...Objective Acute myeloid leukemia(AML)is a highly heterogeneous disease,and molecular events such as DNMT3A gene mutations are associated with poor prognosis in AML patients.Consequently,there is an urgent need for a novel therapeutic approach for AML.Methods DNMT3A mRNA and protein expression were confirmed in DNMT3A-mutant AML cells via RT-qPCR and Western blotting.Cell proliferation and apoptosis were assessed via CCK-8 and Annexin V/PI staining,respectively.Flow cytometry was used to analyze surface antigens and CD44v6 CAR-T-cell transfection efficiency.CD44v6-directed CAR plasmids were constructed,and lentiviruses were packaged.Methylation-specific PCR was used to evaluate differences in promoter methylation,whereas ELISA was used to measure cytokine secretion.Results In this study,we found that the DNMT3A-mutant group presented significantly increased expression of CD44v6 on the cell surface.Methylation of the CD44 promoter region was lower in the mutant group than in the control group.CD44v6 CAR-T cells exhibited specific cytotoxicity against DNMT3A-mutant AML cells.Furthermore,pretreatment with low concentrations of decitabine significantly enhanced the killing effect of CD44v6 CAR-T cells on DNMT3A-mutant AML cells(P<0.05).Additionally,decitabine treatment upregulated the expression of CD44v6 on the surface of DNMT3A-mutant AML cells(P<0.05).Conclusion CD44v6 is a promising CAR-T-cell therapy target in AML patients with DNMT3A mutations.Notably,treatment with decitabine resulted in increased CD44v6 expression on the cell surface of DNMT3A-mutant AML cells.This increase in CD44v6 expression facilitates improved recognition and targeting by CD44v6 CAR-T cells.展开更多
Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocyti...Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.展开更多
AIM:To evaluate the therapeutic effect of folic acid combined with decitabine on diabetic mice.METHODS:The diabetic model of db/db mice were randomly divided into model group,folic acid group,decitabine group,folic ac...AIM:To evaluate the therapeutic effect of folic acid combined with decitabine on diabetic mice.METHODS:The diabetic model of db/db mice were randomly divided into model group,folic acid group,decitabine group,folic acid combined with decitabine group,and C57 mice as normal control group.The density of retinal blood vessels and retinal thickness were detected by fundus photography and optical coherence tomography,respectively.Pathological changes of retina were observed by hematoxylin-eosin(HE)staining.The homocysteine(Hcy)in serum was detected by enzyme linked immunosorbent assay(ELISA).TdT-mediated dUTP nick-end labeling(TUNEL)was used to detect apoptosis in retinal tissue.Evans blue dye was used to detect the permeability of retinal blood vessels.The platelet endothelial cell adhesion molecule-1(CD31)and vascular endothelial growth factor receptor(VEGFR)protein were detected by Western blot.The 3-nitrotyrosine(3-NT)and 4-hydroxynonanine(4-HNE)were detected by immunohistochemistry.RESULTS:The density of retinal blood vessels,retinal thickness,retinal vascular permeability and the proportion of apoptotic cells of retinal tissue in the model group increased significantly than control group(P<0.05).The Hcy in serum and the levels of CD31,VEGFR,3-NT,and 4-HNE in retinal tissue increased significantly in the model group(P<0.01).Folic acid and decitabine both reversed these changes significantly,and the combination of the folic acid and decitabine worked best.CONCLUSION:The combination of folic acid and decitabine has a more significant protective effect on the retina in diabetic mice.展开更多
BACKGROUND Mixed-phenotype acute leukemia(MPAL)is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens.However,consensus regarding the ideal management strategy for ...BACKGROUND Mixed-phenotype acute leukemia(MPAL)is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens.However,consensus regarding the ideal management strategy for MPAL is yet to be established,owing to its rarity.CASE SUMMARY A 55-year-old male was diagnosed with T/myeloid MPAL.Vincristine,prednisolone,daunorubicin,and L-asparaginase were administered as induction chemotherapy.Septic shock occurred 10 days after induction,and bone marrow examination following recovery from sepsis revealed refractory disease.Venetoclax and decitabine were administered as chemotherapy-free induction therapy to reduce the infection risk.There were no serious infections,including febrile neutropenia,at the end of the treatment.After receiving two additional cycles of venetoclax/decitabine,the patient underwent haploidentical peripheral blood stem-cell transplantation and achieved complete response(CR)to treatment.CONCLUSION CR was maintained in a patient with MPAL who underwent haploidentical peripheral blood stem-cell transplantation after additional venetoclax/decitabine cycles.展开更多
Objective:Although the effect of decitabine on myelodysplastic syndrome(MDS)has been demonstrated,merely a proportion of patients respond to therapy,and no well-recognized predictors have been identified.This study wa...Objective:Although the effect of decitabine on myelodysplastic syndrome(MDS)has been demonstrated,merely a proportion of patients respond to therapy,and no well-recognized predictors have been identified.This study was conducted to investigate the effectiveness of decitabine in real-world clinical practice,and determine the predictive factors of response and overall survival(OS)in MDS patients.展开更多
OBJECTIVE: To evaluated the benefits of oral administration of arsenic-containing Qinghuang Powder(QHP)compared with decitabine for patients with high/very-high(H/VH) risk myelodysplastic syndrome(MDS) according to th...OBJECTIVE: To evaluated the benefits of oral administration of arsenic-containing Qinghuang Powder(QHP)compared with decitabine for patients with high/very-high(H/VH) risk myelodysplastic syndrome(MDS) according to the Revised International Prognostic Score System. METHODS: The OS(mOS) rate, annual OS rate and progression to acute myeloid leukemia(AML) in patients with H/VH MDS treated with QHP(QHP group, n = 27) and decitabine(decitabine group, n = 20) were retrospectively analyzed. The effects of prognostic factors of age, proportion of bone marrow blast,peripheral blood cell count, karyotype and Charlson Comorbidity Index(CCI) on OS were further analyzed. RESULTS: The m OS rate of QHP group(29 months) was signi?cantly longer than that of the decitabine group(18 months)(P = 0.043). The OS rates of 1, 2, and 3 years were signi?cantly higher in the QHP group(88.9%, 59.3%, 29.6%) than that in the decitabine group(70%, 25%, and 5%)(P = 0.01). There was no signi?cant difference of 5-year OS rate between the 2 groups(P = 0.133).The effects of prognostic factors on mOS were further analyzed, and it was found that there was no signi?cant difference of m OS rate between the QHP group(29 months) and the decitabine group(21 months) in the patients with age 65 years old(P = 0.673). The mOS rate was signi?cantly longer in QHP group(28.5 months) than that in decitabine group(18 months) in the patients with age of < 65 years old(P = 0.04). The proportions of bone marrow blast cells with 10% or < 10% had no signi?cant effects on the mOS rate of patients in the 2 groups(P = 0.429, P = 0.183). In patients with HGB 80 g/L, mOS rate was signi?cantly longer in the QHP group(57 months) than that in the decitabine group(21 months)(P = 0.047), while in patients with HGB < 80 g/L, there was no signi?cant difference of mOS rate between the 2 groups(P = 0.265). In the patients with PLT < 50×10~9/L, the mOS rate was signi?cantly longer in the QHP group(33 months) than that in the decitabine group(16 months)(P = 0.028). In the patients with PLT 50×10~9/L, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.338). In the patients with ANC < 0.8×10~9/L, the mOS rate was signi?cantly longer in the QHP group(20 months) than that in the decitabine group(7 months)(P = 0.014). In the patients with normal karyotype, the mOS was signi?cantly longer in the QHP group(32 months) than that in the decitabine group(15 months)(P = 0.009). In the patients with abnormal karyotypes, there was no significant difference of the mOS rate between the 2 groups(P = 0.882). In the patients with good karyotypes, the mOS rate was signi?cantly longer in the QHP group(37 months) than that in the decitabine group(20 months)(P = 0.019). In the patients with moderate/poor/very poor karyotype, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.685). In the patients with CCI 3, the mOS rate was signi?cantly longer in the QHP group(34 months) than that in the decitabine group(10.5 months)(P = 0.017). In patients with CCI < 3, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.581). The proportion of progression to AML in the QHP group(18.8%) was signi?cantly lower than that in the decitabine group(25%)(P = 0.03). CONCLUSION: Compared with decitabine, oral administration of arsenic-containing Qinghuang Powder could help patients to survive longer and decrease incidence of progression to acute myeloid leukemia in the treatment of patients with high/very high MDS.展开更多
BACKGROUND Extranodal natural killer/T cell lymphoma,nasal type(ENKL) is a highly aggressive malignancy characterized by its association with Epstein-Barr virus(EBV) and extranodal involvement,which shows a poor clini...BACKGROUND Extranodal natural killer/T cell lymphoma,nasal type(ENKL) is a highly aggressive malignancy characterized by its association with Epstein-Barr virus(EBV) and extranodal involvement,which shows a poor clinical outcome.Although L-asparaginase-based chemotherapy has improved the response rates of relapsed/refractory(R/R) ENKL,relapse occurs in up to 50% of patients with disseminated disease.CASE SUMMARY Immune evasion has emerged as a critical pathway for survival in ENKL and may be effectuated via STAT3-driven upregulation of programmed cell death ligand 1(PD-L1) or other molecular pathways.Anti-PD-1 is effective for R/R ENKL with EBV-driven upregulation of PD-L1 expression.Anti-PD-1 combined with decitabine showed positive preliminary results in a patient with R/R ENKL and resistance to anti-PD-1.CONCLUSION The treatment experience,in this case,demonstrated the potential ability of decitabine combined with PD-1 inhibitor to treat R/R ENKL,thus providing a new treatment strategy for this tumor.展开更多
Objective The aim of the study was to evaluate the clinical efficacy of decitabine(DEC)combined with ruxolitinib(RUX)in the treatment of chronic myelomonocytic leukemia(CMML).Methods The clinical characteristics of 12...Objective The aim of the study was to evaluate the clinical efficacy of decitabine(DEC)combined with ruxolitinib(RUX)in the treatment of chronic myelomonocytic leukemia(CMML).Methods The clinical characteristics of 12 patients with CMML were analyzed retrospectively and subsequent target sequencing was performed to investigate the efficacy of the combined treatment with DEC and RUX and the molecular signatures therein.Results Among the 12 cases,clinical improvement was observed in all patients(100%),spleen reduction was observed in six patients(67%),and hematologic improvement was observed in four patients(33%).In the CMML-1 group,the overall response was 50%(3/6),one case achieved complete response,one achieved bone marrow remission,and one achieved hematological improvement.In the CMML-2 group,the overall response was 17%(1/6),one case achieved complete response,four showed disease progression(PD),and one exhibited no response.As expected,ASXL1 mutation was predictive for the outcome of CMML(hazard ratio of 2.97,95%confidence interval of 1.21–7.06;P=0.02).Conclusion The use of DEC combined with RUX in the treatment of CMML effectively improved the clinical response and quality of life,especially for CMML-1 patients.Ongoing clinical trials will further evaluate the safety and efficacy of this novel therapeutic approach.展开更多
Purpose: Our study was to detect the effect of Decitabine (DAC) combined with arsenic trioxide (AS2O3) on DAPK gene and HL-60 cell proliferation and apoptosis. Methods: DAC and AS2O3 monotherapy, combination treatment...Purpose: Our study was to detect the effect of Decitabine (DAC) combined with arsenic trioxide (AS2O3) on DAPK gene and HL-60 cell proliferation and apoptosis. Methods: DAC and AS2O3 monotherapy, combination treatment and DAC pretreatment were used in this study after incubating with HL-60 cell for 24 h, 48 h, 72 h. CCK8 was used to detect the cell proliferation of HL-60 cell. Flow cytometry was used to detect the cell apoptosis. Then, we used RT-PCR to obtain the gene expression level of DAPK. Results: HL-60 cells were treated with different concentrations of DAC (20 μmol/L, 40 μmol/L, 80 μmol/L), AS2O3 (1 μmol/L, 2.5 μmol/L, 5 μmol/L) monotherapy for 24 h, 48 h, 72 h;along with the extension of the drug concentration and time, proliferation inhibition rate had gradually increased. Monotherapy of DAC, AS2O3 could inhibit the proliferation and induce apoptosis of HL-60 cells, and was time- and dose-dependent. DAC (80 μmol/L) was firstly used for pretreatment, and then, different concentrations of AS2O3 (1 μmol/L, 2.5 μmol/L, 5 μmol/L) were used for 24 h, 48 h, 72 h. It was found that cell proliferation inhibition rate and apoptosis rate had increased significantly. When the two drugs were used together, the increasing proliferation inhibition rate, apoptosis rate and DAPK had become more obvious. Conclusion: DAC and AS2O3 had a synergetic effect for the HL-60 cell proliferation inhibition, apoptosis and expression of DAPK.展开更多
Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)rema...Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)remain major obstacles to a CML cure.In recent years,the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers,including CML,and in turn may be exploited for therapeutic purposes.Here,we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide(AICAR)and decitabine could effectively increase the ATP content and mitochondrial biogenesis.In addition,these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation.Moreover,we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity o f K562 cells to imatinib,as evidenced by a combination treatment assay.Altogether,our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.展开更多
BACKGROUND Simultaneous bilineage hematologic malignancies are rare;however,several cases of acute myeloid leukemia(AML)and T-lymphoblastic lymphoma(T-LBL)cooccurrence have been reported.A standard treatment for simul...BACKGROUND Simultaneous bilineage hematologic malignancies are rare;however,several cases of acute myeloid leukemia(AML)and T-lymphoblastic lymphoma(T-LBL)cooccurrence have been reported.A standard treatment for simultaneous AML and T-LBL has not yet been established,and its prognosis is very poor.Further studies to develop standard treatments are required to increase patient survival rates.CASE SUMMARY A 69-year-old man complaining of pleuritic chest pain visited the emergency room.Computed tomography revealed multiple enlarged lymph nodes(LNs)in the neck and groin and pulmonary thromboembolism with pulmonary infarction.Furthermore,a peripheral blood smear performed due to leukocytosis revealed circulating blasts.Acute myelomonocytic leukemia(AMML)was diagnosed after bone marrow examination,and T-LBL positivity for terminal deoxynucleotidyl transferase,cluster of differentiation(CD)34,and CD4 was confirmed by cervical LN biopsy.Decitabine and dexamethasone were administered because he could not receive intensive chemotherapy due to poor performance status.Complete remission of AMML and T-LBL was achieved after 4 cycles of decitabine plus dexamethasone.CONCLUSION We report the therapeutic effect of decitabine,a hypomethylating agent(HMA),in patients with concurrent bilineage hematologic malignancies and suggest that further studies are required to evaluate the therapeutic effect of HMAs on both lymphoid and bilineage hematologic malignancies.展开更多
This study was conducted to investigate the clinical effect of combining decitabine/azacitidine with HAG in the treatment of single elderly patients with acute myeloid leukemia.Patients in Shaanxi Provincial People’s...This study was conducted to investigate the clinical effect of combining decitabine/azacitidine with HAG in the treatment of single elderly patients with acute myeloid leukemia.Patients in Shaanxi Provincial People’s Hospital were selected for this study from January 2020 to January 2022,and all of the patients were elderly patients with acute myeloid leukemia.Around 23 patients were selected for this study,subsequently the patients were divided into two groups;Group A contained 11 patients and was given decitabine in combination with HAG;and Group B contained 12 patients,and was given azacitidine in combination with HAG.This study showed that the treatment effective rates of patients in both groups were 90.91%and 58.33%,respectively,with a small difference(p>0.05)in the data comparison.The incidence of adverse reactions in the two groups was 63.64%and 16.67%,respectively,with the incidence in group B is significantly(p<0.05)lower compared with group A.Meanwhile,compared with group B,patients in group A had a significantly(p<0.05)shorter mean time to WBC normalization,higher HB and PLT levels,lower WBC levels were lower,all the survival duration times were longer,and subpopulation indicators of peripheral blood T lymphocytes were more in line with normal values.In summary,this study demonstrated that the combination of azacitidine and HAG therapies for the treatment of elderly patients with acute myeloid leukemia is more effective,furthermore can reduce significantly the incidence of adverse treatment effects in patients.展开更多
Objective:To investigate the clinical effects of combining decitabine with a half-dose priming regimen in the treatment of elderly patients with acute myeloid leukemia.Methods:This study was conducted in Shaanxi Provi...Objective:To investigate the clinical effects of combining decitabine with a half-dose priming regimen in the treatment of elderly patients with acute myeloid leukemia.Methods:This study was conducted in Shaanxi Provincial People's Hospital from January 2019 to January 2022.Sxty patients were recruited as the research subects.The patients received different treatments and were randomly divided into two groups,with 30 cases in each group,one of which was treated with conventional priming regimen(control group),and the other was treated with decitabine combined with a half-dose priming regimen(study group).The two groups were compared and analyzed in terms of the effectiveness of treatment.Results:The rate of symptom relief in the study group was 96.67%,which was significantly higher than that in the control group(76.67%)(p<0.05).Before treatment,there was no significant difference in the quality-of-life scores between the two groups,with p>0.05.The patients in the study group had sigificantly longer discase free survival and overall survival than those in the control group,with p<0.05.The effectiveness of treatment in the study group was also better.Conclusion:The use of decitabine im combination with a half dose priming regimen for the treatment of elderly patients with acute myeloid lcukemia is effective in improving patients'quality of life,relieving symptoms.and prolonging their survival.展开更多
目的:探讨在骨髓增生异常综合征(MDS)中TP53基因不同突变状态(野生型/突变型)对地西他滨(DAC)耐药性的影响,并筛选耐药相关调控基因。方法:选用2种TP53状态差异的MDS细胞:M-07e:野生型;SKM-1:突变型,用递增浓度(0、0.5、1、5和10μmol/L...目的:探讨在骨髓增生异常综合征(MDS)中TP53基因不同突变状态(野生型/突变型)对地西他滨(DAC)耐药性的影响,并筛选耐药相关调控基因。方法:选用2种TP53状态差异的MDS细胞:M-07e:野生型;SKM-1:突变型,用递增浓度(0、0.5、1、5和10μmol/L)的地西他滨干预0-72 h后,采用CCK-8法检测细胞活力。通过RNA-Seq转录组测序和甲基化组学分析,筛选与耐药相关的关键基因。结果:CCK-8实验结果显示DAC对M-07e和SKM-1细胞活力的抑制作用呈时间和剂量依赖性(SKM-1耐药性最强,IC_(50)=5μmol/L vs M-07e IC_(50)=0.5μmol/L,P<0.01)。基因表达分析结果显示,M-07e细胞经DAC处理后共鉴定到662个上调基因和452个下调基因;SKM-1细胞经DAC处理后共发现515个上调基因和73个下调基因。蛋白质组学检测显示:DAC处理的M-07e细胞中共鉴定117个上调蛋白和136个下调蛋白;DAC处理的SKM-1细胞中发现91个上调蛋白和46个下调蛋白。通过整合分析上调基因和蛋白表达谱,共筛选出181个候选基因。甲基化组学分析发现884个低甲基化基因中存在高敏感位点和高CpG密度区域,其中与上述181个候选基因存在交集的共31个基因,GO功能富集分析表明这31个基因主要参与细胞分化正调控、结合过程负调控以及细胞组分组织负调控等生物学过程。结论:TP53突变通过表观遗传重编程介导DAC耐药,靶向这些基因可能改善TP53突变型MDS的预后。展开更多
基金supported by the National Natural Science Foundation of China(No.82270177)Chen Xiaoping Foundation for the Development of Science and Technology of Hubei Province(CXPJJH122001-2221).
文摘Objective Acute myeloid leukemia(AML)is a highly heterogeneous disease,and molecular events such as DNMT3A gene mutations are associated with poor prognosis in AML patients.Consequently,there is an urgent need for a novel therapeutic approach for AML.Methods DNMT3A mRNA and protein expression were confirmed in DNMT3A-mutant AML cells via RT-qPCR and Western blotting.Cell proliferation and apoptosis were assessed via CCK-8 and Annexin V/PI staining,respectively.Flow cytometry was used to analyze surface antigens and CD44v6 CAR-T-cell transfection efficiency.CD44v6-directed CAR plasmids were constructed,and lentiviruses were packaged.Methylation-specific PCR was used to evaluate differences in promoter methylation,whereas ELISA was used to measure cytokine secretion.Results In this study,we found that the DNMT3A-mutant group presented significantly increased expression of CD44v6 on the cell surface.Methylation of the CD44 promoter region was lower in the mutant group than in the control group.CD44v6 CAR-T cells exhibited specific cytotoxicity against DNMT3A-mutant AML cells.Furthermore,pretreatment with low concentrations of decitabine significantly enhanced the killing effect of CD44v6 CAR-T cells on DNMT3A-mutant AML cells(P<0.05).Additionally,decitabine treatment upregulated the expression of CD44v6 on the surface of DNMT3A-mutant AML cells(P<0.05).Conclusion CD44v6 is a promising CAR-T-cell therapy target in AML patients with DNMT3A mutations.Notably,treatment with decitabine resulted in increased CD44v6 expression on the cell surface of DNMT3A-mutant AML cells.This increase in CD44v6 expression facilitates improved recognition and targeting by CD44v6 CAR-T cells.
基金supported by grants from the National Natural Science Foundation of China(No.81300412 and No.81470333)
文摘Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.
基金Supported by the Natural Science Foundation of Gansu Province(No.21JR7RA361).
文摘AIM:To evaluate the therapeutic effect of folic acid combined with decitabine on diabetic mice.METHODS:The diabetic model of db/db mice were randomly divided into model group,folic acid group,decitabine group,folic acid combined with decitabine group,and C57 mice as normal control group.The density of retinal blood vessels and retinal thickness were detected by fundus photography and optical coherence tomography,respectively.Pathological changes of retina were observed by hematoxylin-eosin(HE)staining.The homocysteine(Hcy)in serum was detected by enzyme linked immunosorbent assay(ELISA).TdT-mediated dUTP nick-end labeling(TUNEL)was used to detect apoptosis in retinal tissue.Evans blue dye was used to detect the permeability of retinal blood vessels.The platelet endothelial cell adhesion molecule-1(CD31)and vascular endothelial growth factor receptor(VEGFR)protein were detected by Western blot.The 3-nitrotyrosine(3-NT)and 4-hydroxynonanine(4-HNE)were detected by immunohistochemistry.RESULTS:The density of retinal blood vessels,retinal thickness,retinal vascular permeability and the proportion of apoptotic cells of retinal tissue in the model group increased significantly than control group(P<0.05).The Hcy in serum and the levels of CD31,VEGFR,3-NT,and 4-HNE in retinal tissue increased significantly in the model group(P<0.01).Folic acid and decitabine both reversed these changes significantly,and the combination of the folic acid and decitabine worked best.CONCLUSION:The combination of folic acid and decitabine has a more significant protective effect on the retina in diabetic mice.
文摘BACKGROUND Mixed-phenotype acute leukemia(MPAL)is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens.However,consensus regarding the ideal management strategy for MPAL is yet to be established,owing to its rarity.CASE SUMMARY A 55-year-old male was diagnosed with T/myeloid MPAL.Vincristine,prednisolone,daunorubicin,and L-asparaginase were administered as induction chemotherapy.Septic shock occurred 10 days after induction,and bone marrow examination following recovery from sepsis revealed refractory disease.Venetoclax and decitabine were administered as chemotherapy-free induction therapy to reduce the infection risk.There were no serious infections,including febrile neutropenia,at the end of the treatment.After receiving two additional cycles of venetoclax/decitabine,the patient underwent haploidentical peripheral blood stem-cell transplantation and achieved complete response(CR)to treatment.CONCLUSION CR was maintained in a patient with MPAL who underwent haploidentical peripheral blood stem-cell transplantation after additional venetoclax/decitabine cycles.
基金This work was supported by the National Natural Science Foundation of China(No.81770168 and No.81570110).
文摘Objective:Although the effect of decitabine on myelodysplastic syndrome(MDS)has been demonstrated,merely a proportion of patients respond to therapy,and no well-recognized predictors have been identified.This study was conducted to investigate the effectiveness of decitabine in real-world clinical practice,and determine the predictive factors of response and overall survival(OS)in MDS patients.
基金supported by National Natural Science Foundation of China(81673821)National Natural Science Foundation of China(81774142)+1 种基金Central Level Research Institute of Public Welfare Research Funds(ZZ10-016)National TCM Clinical Research Base Business Construction Second Batch of Scientific Research Projects(JDZX2015264)
文摘OBJECTIVE: To evaluated the benefits of oral administration of arsenic-containing Qinghuang Powder(QHP)compared with decitabine for patients with high/very-high(H/VH) risk myelodysplastic syndrome(MDS) according to the Revised International Prognostic Score System. METHODS: The OS(mOS) rate, annual OS rate and progression to acute myeloid leukemia(AML) in patients with H/VH MDS treated with QHP(QHP group, n = 27) and decitabine(decitabine group, n = 20) were retrospectively analyzed. The effects of prognostic factors of age, proportion of bone marrow blast,peripheral blood cell count, karyotype and Charlson Comorbidity Index(CCI) on OS were further analyzed. RESULTS: The m OS rate of QHP group(29 months) was signi?cantly longer than that of the decitabine group(18 months)(P = 0.043). The OS rates of 1, 2, and 3 years were signi?cantly higher in the QHP group(88.9%, 59.3%, 29.6%) than that in the decitabine group(70%, 25%, and 5%)(P = 0.01). There was no signi?cant difference of 5-year OS rate between the 2 groups(P = 0.133).The effects of prognostic factors on mOS were further analyzed, and it was found that there was no signi?cant difference of m OS rate between the QHP group(29 months) and the decitabine group(21 months) in the patients with age 65 years old(P = 0.673). The mOS rate was signi?cantly longer in QHP group(28.5 months) than that in decitabine group(18 months) in the patients with age of < 65 years old(P = 0.04). The proportions of bone marrow blast cells with 10% or < 10% had no signi?cant effects on the mOS rate of patients in the 2 groups(P = 0.429, P = 0.183). In patients with HGB 80 g/L, mOS rate was signi?cantly longer in the QHP group(57 months) than that in the decitabine group(21 months)(P = 0.047), while in patients with HGB < 80 g/L, there was no signi?cant difference of mOS rate between the 2 groups(P = 0.265). In the patients with PLT < 50×10~9/L, the mOS rate was signi?cantly longer in the QHP group(33 months) than that in the decitabine group(16 months)(P = 0.028). In the patients with PLT 50×10~9/L, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.338). In the patients with ANC < 0.8×10~9/L, the mOS rate was signi?cantly longer in the QHP group(20 months) than that in the decitabine group(7 months)(P = 0.014). In the patients with normal karyotype, the mOS was signi?cantly longer in the QHP group(32 months) than that in the decitabine group(15 months)(P = 0.009). In the patients with abnormal karyotypes, there was no significant difference of the mOS rate between the 2 groups(P = 0.882). In the patients with good karyotypes, the mOS rate was signi?cantly longer in the QHP group(37 months) than that in the decitabine group(20 months)(P = 0.019). In the patients with moderate/poor/very poor karyotype, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.685). In the patients with CCI 3, the mOS rate was signi?cantly longer in the QHP group(34 months) than that in the decitabine group(10.5 months)(P = 0.017). In patients with CCI < 3, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.581). The proportion of progression to AML in the QHP group(18.8%) was signi?cantly lower than that in the decitabine group(25%)(P = 0.03). CONCLUSION: Compared with decitabine, oral administration of arsenic-containing Qinghuang Powder could help patients to survive longer and decrease incidence of progression to acute myeloid leukemia in the treatment of patients with high/very high MDS.
基金Supported by the Medical Health Science and Technology Project of Zhejiang Province Health Commission,No.2020376298。
文摘BACKGROUND Extranodal natural killer/T cell lymphoma,nasal type(ENKL) is a highly aggressive malignancy characterized by its association with Epstein-Barr virus(EBV) and extranodal involvement,which shows a poor clinical outcome.Although L-asparaginase-based chemotherapy has improved the response rates of relapsed/refractory(R/R) ENKL,relapse occurs in up to 50% of patients with disseminated disease.CASE SUMMARY Immune evasion has emerged as a critical pathway for survival in ENKL and may be effectuated via STAT3-driven upregulation of programmed cell death ligand 1(PD-L1) or other molecular pathways.Anti-PD-1 is effective for R/R ENKL with EBV-driven upregulation of PD-L1 expression.Anti-PD-1 combined with decitabine showed positive preliminary results in a patient with R/R ENKL and resistance to anti-PD-1.CONCLUSION The treatment experience,in this case,demonstrated the potential ability of decitabine combined with PD-1 inhibitor to treat R/R ENKL,thus providing a new treatment strategy for this tumor.
基金Supported by a grant from the Fund of Ruijin Hospital North affiliated to Shanghai Jiao Tong University School of Medicine(No:2018ZY03)
文摘Objective The aim of the study was to evaluate the clinical efficacy of decitabine(DEC)combined with ruxolitinib(RUX)in the treatment of chronic myelomonocytic leukemia(CMML).Methods The clinical characteristics of 12 patients with CMML were analyzed retrospectively and subsequent target sequencing was performed to investigate the efficacy of the combined treatment with DEC and RUX and the molecular signatures therein.Results Among the 12 cases,clinical improvement was observed in all patients(100%),spleen reduction was observed in six patients(67%),and hematologic improvement was observed in four patients(33%).In the CMML-1 group,the overall response was 50%(3/6),one case achieved complete response,one achieved bone marrow remission,and one achieved hematological improvement.In the CMML-2 group,the overall response was 17%(1/6),one case achieved complete response,four showed disease progression(PD),and one exhibited no response.As expected,ASXL1 mutation was predictive for the outcome of CMML(hazard ratio of 2.97,95%confidence interval of 1.21–7.06;P=0.02).Conclusion The use of DEC combined with RUX in the treatment of CMML effectively improved the clinical response and quality of life,especially for CMML-1 patients.Ongoing clinical trials will further evaluate the safety and efficacy of this novel therapeutic approach.
文摘Purpose: Our study was to detect the effect of Decitabine (DAC) combined with arsenic trioxide (AS2O3) on DAPK gene and HL-60 cell proliferation and apoptosis. Methods: DAC and AS2O3 monotherapy, combination treatment and DAC pretreatment were used in this study after incubating with HL-60 cell for 24 h, 48 h, 72 h. CCK8 was used to detect the cell proliferation of HL-60 cell. Flow cytometry was used to detect the cell apoptosis. Then, we used RT-PCR to obtain the gene expression level of DAPK. Results: HL-60 cells were treated with different concentrations of DAC (20 μmol/L, 40 μmol/L, 80 μmol/L), AS2O3 (1 μmol/L, 2.5 μmol/L, 5 μmol/L) monotherapy for 24 h, 48 h, 72 h;along with the extension of the drug concentration and time, proliferation inhibition rate had gradually increased. Monotherapy of DAC, AS2O3 could inhibit the proliferation and induce apoptosis of HL-60 cells, and was time- and dose-dependent. DAC (80 μmol/L) was firstly used for pretreatment, and then, different concentrations of AS2O3 (1 μmol/L, 2.5 μmol/L, 5 μmol/L) were used for 24 h, 48 h, 72 h. It was found that cell proliferation inhibition rate and apoptosis rate had increased significantly. When the two drugs were used together, the increasing proliferation inhibition rate, apoptosis rate and DAPK had become more obvious. Conclusion: DAC and AS2O3 had a synergetic effect for the HL-60 cell proliferation inhibition, apoptosis and expression of DAPK.
文摘Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)remain major obstacles to a CML cure.In recent years,the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers,including CML,and in turn may be exploited for therapeutic purposes.Here,we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide(AICAR)and decitabine could effectively increase the ATP content and mitochondrial biogenesis.In addition,these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation.Moreover,we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity o f K562 cells to imatinib,as evidenced by a combination treatment assay.Altogether,our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.
文摘BACKGROUND Simultaneous bilineage hematologic malignancies are rare;however,several cases of acute myeloid leukemia(AML)and T-lymphoblastic lymphoma(T-LBL)cooccurrence have been reported.A standard treatment for simultaneous AML and T-LBL has not yet been established,and its prognosis is very poor.Further studies to develop standard treatments are required to increase patient survival rates.CASE SUMMARY A 69-year-old man complaining of pleuritic chest pain visited the emergency room.Computed tomography revealed multiple enlarged lymph nodes(LNs)in the neck and groin and pulmonary thromboembolism with pulmonary infarction.Furthermore,a peripheral blood smear performed due to leukocytosis revealed circulating blasts.Acute myelomonocytic leukemia(AMML)was diagnosed after bone marrow examination,and T-LBL positivity for terminal deoxynucleotidyl transferase,cluster of differentiation(CD)34,and CD4 was confirmed by cervical LN biopsy.Decitabine and dexamethasone were administered because he could not receive intensive chemotherapy due to poor performance status.Complete remission of AMML and T-LBL was achieved after 4 cycles of decitabine plus dexamethasone.CONCLUSION We report the therapeutic effect of decitabine,a hypomethylating agent(HMA),in patients with concurrent bilineage hematologic malignancies and suggest that further studies are required to evaluate the therapeutic effect of HMAs on both lymphoid and bilineage hematologic malignancies.
文摘This study was conducted to investigate the clinical effect of combining decitabine/azacitidine with HAG in the treatment of single elderly patients with acute myeloid leukemia.Patients in Shaanxi Provincial People’s Hospital were selected for this study from January 2020 to January 2022,and all of the patients were elderly patients with acute myeloid leukemia.Around 23 patients were selected for this study,subsequently the patients were divided into two groups;Group A contained 11 patients and was given decitabine in combination with HAG;and Group B contained 12 patients,and was given azacitidine in combination with HAG.This study showed that the treatment effective rates of patients in both groups were 90.91%and 58.33%,respectively,with a small difference(p>0.05)in the data comparison.The incidence of adverse reactions in the two groups was 63.64%and 16.67%,respectively,with the incidence in group B is significantly(p<0.05)lower compared with group A.Meanwhile,compared with group B,patients in group A had a significantly(p<0.05)shorter mean time to WBC normalization,higher HB and PLT levels,lower WBC levels were lower,all the survival duration times were longer,and subpopulation indicators of peripheral blood T lymphocytes were more in line with normal values.In summary,this study demonstrated that the combination of azacitidine and HAG therapies for the treatment of elderly patients with acute myeloid leukemia is more effective,furthermore can reduce significantly the incidence of adverse treatment effects in patients.
基金Basic Research of Natural Science in Shaanxi Province(Grant Number:2021JM-548)SPPH Incubator Fund for Development of Science and Technology(Grant Number:2021YJY-19)。
文摘Objective:To investigate the clinical effects of combining decitabine with a half-dose priming regimen in the treatment of elderly patients with acute myeloid leukemia.Methods:This study was conducted in Shaanxi Provincial People's Hospital from January 2019 to January 2022.Sxty patients were recruited as the research subects.The patients received different treatments and were randomly divided into two groups,with 30 cases in each group,one of which was treated with conventional priming regimen(control group),and the other was treated with decitabine combined with a half-dose priming regimen(study group).The two groups were compared and analyzed in terms of the effectiveness of treatment.Results:The rate of symptom relief in the study group was 96.67%,which was significantly higher than that in the control group(76.67%)(p<0.05).Before treatment,there was no significant difference in the quality-of-life scores between the two groups,with p>0.05.The patients in the study group had sigificantly longer discase free survival and overall survival than those in the control group,with p<0.05.The effectiveness of treatment in the study group was also better.Conclusion:The use of decitabine im combination with a half dose priming regimen for the treatment of elderly patients with acute myeloid lcukemia is effective in improving patients'quality of life,relieving symptoms.and prolonging their survival.
文摘目的:探讨在骨髓增生异常综合征(MDS)中TP53基因不同突变状态(野生型/突变型)对地西他滨(DAC)耐药性的影响,并筛选耐药相关调控基因。方法:选用2种TP53状态差异的MDS细胞:M-07e:野生型;SKM-1:突变型,用递增浓度(0、0.5、1、5和10μmol/L)的地西他滨干预0-72 h后,采用CCK-8法检测细胞活力。通过RNA-Seq转录组测序和甲基化组学分析,筛选与耐药相关的关键基因。结果:CCK-8实验结果显示DAC对M-07e和SKM-1细胞活力的抑制作用呈时间和剂量依赖性(SKM-1耐药性最强,IC_(50)=5μmol/L vs M-07e IC_(50)=0.5μmol/L,P<0.01)。基因表达分析结果显示,M-07e细胞经DAC处理后共鉴定到662个上调基因和452个下调基因;SKM-1细胞经DAC处理后共发现515个上调基因和73个下调基因。蛋白质组学检测显示:DAC处理的M-07e细胞中共鉴定117个上调蛋白和136个下调蛋白;DAC处理的SKM-1细胞中发现91个上调蛋白和46个下调蛋白。通过整合分析上调基因和蛋白表达谱,共筛选出181个候选基因。甲基化组学分析发现884个低甲基化基因中存在高敏感位点和高CpG密度区域,其中与上述181个候选基因存在交集的共31个基因,GO功能富集分析表明这31个基因主要参与细胞分化正调控、结合过程负调控以及细胞组分组织负调控等生物学过程。结论:TP53突变通过表观遗传重编程介导DAC耐药,靶向这些基因可能改善TP53突变型MDS的预后。
