Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). Methods The ratio of the bone marrow cells with abnormal chromosomes to the total ...Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). Methods The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor (TNF), CD4^+ and CD8^+ T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed. Results The clone burden of MDS patients was 67.4%±36.2%. MDS clone burden positively correlated with bone marrow blasts (r = 0.483, P<0.05), negatively with hemoglobin level (r=-0.445, P<0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (>50%) and low clone burden (≤50%) groups were 7.78%±5.51% and 3.45%±3.34%, 56.06±14.28 g/L and 76.40±24.44 g/L, (1.82±0.48)×10~ 12 /L and (2.32±0.66)×10~ 12 /L, respectively (all P<0.05). CD4^+ T lymphocytes of MDS patients and normal controls were (0.274±0.719)×10~ 9 /L and (0.455±0.206)×10~ 9 /L, respectively (P<0.05). CD8^+ T lymphocytes of MDS patients and normal controls were (0.240±0.150)×10~ 9 /L and (0.305±0.145)×10~ 9 /L, respectively. The serum level of interleukin-2 of MDS patients (6.29±3.58 ng/mL) was significantly higher than normal control (3.11±1.40 ng/mL, P<0.05). The serum level of TNF of MDS patients and normal control group were 2.42±1.79 ng/mL and 1.68±0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90±0.52) than that in low clone burden patients (0.97±0.44, P<0.05). Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its progression.展开更多
Objective This study aims to investigate the expression of delta-like 1 （DLK1） gene in the bone marrow cells of patients with myelodysplastic syndromes （MDS） and to explore its molecular characteristics for the ea...Objective This study aims to investigate the expression of delta-like 1 （DLK1） gene in the bone marrow cells of patients with myelodysplastic syndromes （MDS） and to explore its molecular characteristics for the early diagnosis of MDS. Methods The expression of DLK1 mRNA in the bone marrow cells of cases with MDS, acute myeloid leukemia （AML）, and normal control groups were measured by real-time polymerase chain reaction and were analyzed for clinical significance. Results Significantly higher expression of DLK1 mRNA was observed in the bone marrow cells of MDS patients （0.7342±0.3652） compared with the normal control group （0.4801±0.1759） （P〈0.05）. The expression of DLK1 mRNA had a positive correlation with the proportion of bone marrow blasts （r=0.467, P〈0.05）. Moreover, DLK1 mRNA expression was significantly increased as MDS progressed （P〈0.05）. Patients with abnormal karyotypes exhibited significantly higher expression of DLK1 mRNA （0.9007±0.4334） than those with normal karyotypes （0.6411±0.2630） （P〈0.05）. Subsequently, patients with highly expressed DLK1 （≥0.8） presented significantly higher malignant clone burden （0.4134±0.3999） than those with lower DLK1 expression （〈0.8）,（0.1517±0.3109）, （P〈0.05）. Conclusions The DLK1 gene was highly expressed in MDS patients, and was increased as MDS progressed. The expression of DLK1 mRNA was positively correlated with the proportion of the bone marrow blasts. A high expression of DLK1 gene suggested a higher malignant clone burden of MDS.展开更多
Sekeres et al. （1） conducted a multicenter randomized, controlled trial to compare whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates to azacitidine in the...Sekeres et al. （1） conducted a multicenter randomized, controlled trial to compare whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates to azacitidine in the treatment of myelodysplastic syndromes （MDS）. In that trial, 224 patients with higher-risk MDS and 53 with chronic myelomonocytic leukemia （CMML） were enrolled and randomly assigned to the ＂azacitidine＂ group, ＂azacitidine plus lenalidomide＂ group or ＂azacitidine plus vorinostat＂ group. The researchers found that patients with MDS treated with azacitidine-based combinations had similar response rate to azacitidine monotherapy. Using genomic mutation analysis, they found that the overall response rate to azacitidine-based treatment was higher for patients with mutations in DNMT3A and lower for those with mutations in SRSF2. Whereas in another study, Welch et al. enrolled 26 patients with MDS and 90 with acute myeloid leukemia （AML） who were treated with decitabine, and they found that patients with TP53 mutations had a higher response rate, but not those with DNMT3A mutations （2）. We propose that this big discrepancy in the conclusions between the two studies might have been caused by the presence of many co-interacting factors, e.g. study aims, DNA demethylating agents, treatment protocols, and patient sources.展开更多
Myelodysplastic syndrome(MDS)is a malignant clonal disease of human hematopoietic stem cells.In this paper,a case of MDS with fever and rash as the first symptom was reported in our hospital,and the related literature...Myelodysplastic syndrome(MDS)is a malignant clonal disease of human hematopoietic stem cells.In this paper,a case of MDS with fever and rash as the first symptom was reported in our hospital,and the related literature was reviewed and summarized to provide ideas for the diagnosis of MDS.Case summary:The patient,male,62 years old,with systemic rash and fever as the initial symptoms,early multiple bone marrow examination showed no typical abnormalities.With the progress of the disease,bone marrow cytology,flow cytometry,molecular karyotype,chromosomal karyotype,skin biopsy and pathological diagnosis were performed,and the diagnosis was MDS.展开更多
Background:Oral administration of indigo naturalis(IN)is used as a complementary and alternative medicine(CAM)regimen for the treatment of myelodysplastic syndromes(MDS).However,its mechanism of action has not been fu...Background:Oral administration of indigo naturalis(IN)is used as a complementary and alternative medicine(CAM)regimen for the treatment of myelodysplastic syndromes(MDS).However,its mechanism of action has not been fully elucidated and needs to be further explored.Methods:By searching the traditional Chinese medicine system and analyzing platforms(TCMSP),bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine(BATMAN-TCM),and Swiss Target Prediction network database,the main active components and potential targets of IN were obtained.Based on this,a component-target network was established by Cytoscape 3.6.1 software.Differentially expressed genes(DGEs)in MDS were obtained from three GEO(Gene Expression Omnibus)gene chips.Then,the protein-protein interaction(PPI)network of DGEs was constructed and analyzed by STRING database and Cytoscape 3.6.1 software.In addition,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)biological enrichment analysis were carried out using REVIGO and KEGG Orthology Based Annotation System(KOBAS)on DGEs,respectively.Identification of IN-MDS compound targets was performed by matching potential targets of active components with disease-related targets.The results of KEGG pathway enrichment analysis were combined with compound targets to screen key targets.In the end,molecular docking was performed by SYBYL-X2.1 to verify the key targets.Results:Nine active components of IN and 439 potential targets of IN were identified by analyzing TCMSP,BATMAN-TCM,and Swiss Target Prediction network databases.Three MDS disease-related gene microarray chips were obtained from the GEO databases:GSE4619,GSE19429,and GSE58831.Through this analysis,87 DEGs were finally obtained using the Venn diagram.A PPI network of DEGs was then constructed,in which 18 genes were upregulated and 69 genes were downregulated.After the GO enrichment results were de-redundant,the representative GO terms were obtained by using REVIGO semantic similarity measuremen.The KEGG biological pathway analysis using the KOBAS indicated that the Hippo signaling pathway is important in MDS.The Hippo signaling pathway involves four genes:AREG,LEF1,SMAD7,and TCF4.By matching and mapping DEGs with potential targets,six IN-MDS compound targets were obtained:PDE4B,PLAUR,ELANE,NR3C1,AREG,and LEF1.We found that AREG and LEF1 are consistent with the genes involved in the Hippo signaling pathway.Through molecular docking simulation,we found that the indican binds best to AREG and LEF1.Conclusion:Based on the integrated pharmacology model,the material basis of the efficacy and biological molecular mechanism of IN in the treatment of MDS was systematically studied,which provided a novel indication of the CAM regimen for the improvement of MDS management.展开更多
Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells （BMMNC） of patients with myelodysplastic syndrome （MDS） and its clinical significance. Methods The expression o...Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells （BMMNC） of patients with myelodysplastic syndrome （MDS） and its clinical significance. Methods The expression of TET2 mRNA and protein in bone marrow mononuclear cells （BMMNC） of 32 patients with MDS and 20 healthy donors was examined by qPCR and Western blot. Results The expression of TET2 mRNA in BMMNC was down-regulated in MDS patients compared with the donor group [（0.41±0.28）% vs. （1.07±0.56）%] （P〈0.001）. Compared with lower expression group （TET2〈0.4） [（6.53±6.17）%], patients with higher expression of TET2 ≥0.4） presented significantly lower proportion of bone marrow blasts [（1.21±1.56）%1 （P〈0.05）. The expression of TET2 mRNA in BMMNC of MDS patients was inversely correlated with malignant clone burden （t=--0.398, P〈0.05） and IPSS r=-0.412, P〈0.05）. The expression of TET2 protein was down-regulated in MDS patients compared with that in the donor group. Conclusions The mRNA and protein expression of TET2 in BMMNC of MDS patients is decreased, which might be useful as an important parameter for the evaluation of MDS clone burden.展开更多
Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of...Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of MDS: (1) Conventional Cytogenetics (CC) for clonal chromosomal abnormalities; (2) BrdU-Sister Chromatid Differentiation (BrdU-SCD) for cell cycle kinetics; (3) Fluorescence in Situ Hybridization (FISH) for trisomy 8; (4) Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) for N-ras mutation. Results: The diagnosis of forty-three patients was compatible with the FAB criteria for MDS. The other seven cases didn’t meet the FAB criteria, with only one lineage of dyspoiesis or with no obvious dysplastic changes. Among these seven cases, two were morphologically diagnosed with suspicious refractory anemia, one with sideroblastic anemia, one with leukemoid reaction, one with hypercellular anemia and two with chronic aplastic anemia. Clonal analyses of the 7 patients showed that six cases had clonal karyotype abnormalities, four had prolonged cell cycle patterns, four had trisomy 8 of different proportions and one had mutation of the exon 1 of N-RAS. Thus, they were revaluated as MDS patients. Conclusion: The untypical MDS patients with one lineage dyspoiesis or without obvious dysplastic changes can be diagnosed early by combining multiple clonal analysis techniques such as CC, SCD, FISH and PCR-SSCR.展开更多
OBJECTIVE Some mtDNA mutations have been detected in patients with myelodysplastic syndromes(MDSs).As the non-coding region of mitochondria,the displacement loop(D-loop) region of mtDNA contains important elements for...OBJECTIVE Some mtDNA mutations have been detected in patients with myelodysplastic syndromes(MDSs).As the non-coding region of mitochondria,the displacement loop(D-loop) region of mtDNA contains important elements for mtDNA replication and transcription.Variants of the D-loop region were found to be related to the cause of many diseases.The aim of our study was to investigate mutations and single nucleotide polymorphisms in the D-loop region of MDS patients.METHODS The mutations and SNPs in the hypervariable regions of the D-loop were detected by direct sequencing in MDS patients and normal controls.RESULTS Sixty-four SNPs were found in the D-loop region in MDS cases and control group.Among the SNPs,the 16,189 variant(T > C transition) was found to have an increased frequency in the MDS group(P = 0.044).However,no mutations were detected in neither group.CONCLUSION Our data provide evidence for a highly polymorphic D-loop region in patients with MDS,but do not support the presence of mutations in the mitochondrial D-loop region in MDS cases.The mtDNA T16,189C variant,which may be a functional variant,is associated with increased susceptibility to a MDS.展开更多
OBJECTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MDS).METHODS:Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor po...OBJECTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MDS).METHODS:Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor potential of YSG and its safety,assess its effect on overall survival(OS),and evaluate whether its mechanism is associated with the demethylation of the secreted frizzled related protein 5(s FRP5)gene and suppressing Wnt/β-catenin pathway.Bisulfite amplicon sequencing was applied to detect the level of methylation of the s FRP5 gene;western blotting,immunofluorescence staining,and real-time Polymerase Chain Reaction were performed to detect DNA methyltransferase 1(DNMT1),s FRP5,and other Wnt/β-catenin pathway-related m RNA and protein expression.RESULTS:The results showed that high-dosage YSG exerted an anti-tumor effect similar to that of decitabine,improved OS,and reduced long-term adverse effects in the long term.Mechanically,YSG reduced the expression of DNMT1 methyltransferase,decreased the methylation,and increased the expression of the Wnt/β-catenin pathway antagonist-s FRP5.Furthermore,components of the Wnt/β-catenin pathway,including Wnt3a,β-catenin,c-Myc,and cyclin D1,were down-regulated in response to YSG,suggesting that YSG could treat MDS by demethylating the s FRP5 gene and suppressing the Wnt/β-catenin pathway.CONCLUSIONS:Our findings demonstrated that YSG could be used alone or in combination with decitabine to improve outcomes in the MDS animal model,providing an alternative solution for treating MDS.展开更多
Objective To determine the expression and function of the c-kit receptor in bone marrow mononuclear cells (BMMNC) of patients with myelodysplastic syndromes (MDS). Methods Direct immunofluorescence assay and reverse t...Objective To determine the expression and function of the c-kit receptor in bone marrow mononuclear cells (BMMNC) of patients with myelodysplastic syndromes (MDS). Methods Direct immunofluorescence assay and reverse transcriptase-polymerase chain reaction (RTPCR) were used to detect c-kit protein and c-kit mRNA expressions in the BMMNC of 29 MDS patients and 10 normal controls. Cell culture was used to detect the function of the c-kit receptor. Results c-kit protein expression in the MDS group was significantly higher than that in the control group (8.58％ +5.28％ vs 3.04％ + 1.49％, P＜0.05). c-kit protien expression in the refractory anemia (RA)group was significantly lower than that in the RA with an excess of blasts (RAEB)/RAEB in transformation (RAEB-t) group (5.12％ +2.13％ vs 10.01％ +5.07％, P＜0.05). The rate of c-kit protein expression was 32.43％ in aoute myeloblastic leukemia (AML) cases transformed from MDS (t-AML). c-kit mRNA expression in the MDS group was correlated with c-kit protein expression. Interieukin-3 (IL-3) and erythropoietin (Epo), with or without stem cell factor (SCF), upregulated c-kit protein and its mRNA expression. In the presence of IL-3 and Epo, SCF showed significant stimulating effects on the formation of CFU-GM and BFU-E in semi-solid cultures of normal BMMNC, but had no effects on those of the MDS patients.Conclusion The protein and mRNA expression of the c-kit receptor in the BMMNC of MDS patients were higher than those of normal controls, and the function of this receptor in MDS BMMNC was abnormal. Chin Med J 2001; 114(5) :481-485展开更多
Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemi...Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.Results During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1-23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M 2, M 4, or M 5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD 33 [(49.83±24.50)%], CD 13 [(36.38±33.84)%], monocytic antigen CD 14 [(38.50±24.60)%], and stem cell marker CD 34 [(34.67±30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD 5, CD 7, CD 9, and CD 19, coexisted with myeloid antigens. A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1-28) months, were found in patients with MDS-AML treated by induction chemotherapy.Conclusions MDS has a high risk of developing into AML, either gradually or rapidly. Patients with MDS-AML have specific biological characteristics and a worse prognosis.展开更多
The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classif...The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia(a CML), chronic myelomonocytic leukemia(CMML), juvenile myelomonocytic leukemia(JMML), MDS/MPN-unclassifiable(MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis(RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of nextgeneration platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis,prognostication, and treatment. Future goals of research should include the development of disease-modifying therapies, and further genetic understanding of the category will likely form the foundation of these efforts.展开更多
OBJECTIVE:To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia(MDS-MLD)and arsenic concentration in the peripheral blood of patients.ME...OBJECTIVE:To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia(MDS-MLD)and arsenic concentration in the peripheral blood of patients.METHODS:In this prospective study,a total of 50 MDS-MLD patients were treated with traditional Chinese drugs containing realgar for 3 months in Xiyuan Hospital from March 2018 to January 2019.Routine blood examination as well as liver and kidney function were monitored before and after treatment.The concentration of arsenic in the peripheral blood was measured using an atomic fluorescence spectrometer after treatment.The correlation between clinical effect and arsenic concentration was analyzed by Spearman’s method.RESULTS:The treatment response rate was 54%.Two patients(4%)achieved complete remission,50%(25 of 50)showed hematologic improvement,and 23 patients had stable disease(23%).No disease progression was observed.Arsenic concentration in the peripheral blood ranged from 14.60 to 85.96μg/L.Clinical efficacy was positively correlated with arsenic concentration(P<0.05).The incidence of mild adverse reactions was 16%.CONCLUSION:A relatively high concentration of arsenic in the peripheral blood may improve the clinical efficacy of realgar in MDS-MLD patients.展开更多
Myelodysplastic syndromes （MDS） are a heterogeneous group of clonal disorderscharacterized by ineffective hematopoiesis; they manifest clinically as anemia, neutropenia, and thrombocytopenia.1＇2 Higher risk MDS inc...Myelodysplastic syndromes （MDS） are a heterogeneous group of clonal disorderscharacterized by ineffective hematopoiesis; they manifest clinically as anemia, neutropenia, and thrombocytopenia.1＇2 Higher risk MDS include patients in the intermediate-2 and high-risk categories of the International Prognostic Scoring System （IPSS）, as well as patients with MDS secondary to radiation or chemical exposure.3 The patients with higher risk MDS have a peculiar propensity to evolve into acute myeloid leukemia （AML）, and have a median survival of 〈12 months.4 Management of higher risk MDS varies from supportive care with transfusions or hematopoietic cytokines to high-intensity3 chemotherapy or hematopoietic stem cell transplantation. The impact of intensive myelosuppressive chemotherapy, similar to AML induction therapy, has been investigated. The results are comparable to the reported outcome of patients with AML, i.e. complete remission （CR） rates of 40%-60% and median overall survival （OS） of 8-12 months,s Thus, innovative approaches are needed for the treatment of higher risk MDS.展开更多
OBJECTIVE: To explore the immunophenotype of myeloid cells in myelodysplastic syndyomes (MDS) and its clinical implications. METHODS: A panel of monoclonal antibody was used to detect CD13+, CD33+, CD15+ and CD14+ ant...OBJECTIVE: To explore the immunophenotype of myeloid cells in myelodysplastic syndyomes (MDS) and its clinical implications. METHODS: A panel of monoclonal antibody was used to detect CD13+, CD33+, CD15+ and CD14+ antigens on the membrane surfaces of myeloid cells in the bone marrow from 51 MDS, 21 aplastic anemia (AA), 21 paroxysmal nocturnal hemoglobinuria (PNH) patients. 10 acute myeloblastic leukemia (AML) patients and 15 normal subjects by immunoenzymatic assay. The morphology and chromosome karyotype of bone marrow cells of MDS patients were also examined. RESULTS: CD14+, CD13+ and CD33+ cells in the bone marrow were more in MDS patients than in normal controls, AA patients and PNH patients. CD15+ cells in the bone marrow were less in MDS patients than in normal controls. CONCLUSIONS: The percentages of CD14+, CD13+ and CD33+ positive cells in the bone marrow of MDS patients were related to the percentage of myeloblasts, the chromosomal aberrations and the response to treatment. It indicated that there is immunophenotypic misexpression of myeloid cells in MDS patients. Immunophenotype analysis of myeloid cells might be useful for the diagnosis and treatment of MDS patients.展开更多
DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes(MDS).Aberrant DNA methylation represses the transcription of promotors of tumor suppressor ...DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes(MDS).Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes,inducing gene silencing.Realgar(α-As_(4)S_(4))is a traditional medicine used for the treatment of various diseases in the ancient time.Realgar was reported to have efficacy for acute promyelocytic leukemia(APL).It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS.This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS,as well as the species and metabolisms of arsenic in vivo.展开更多
Qinghuang Powder(QHP),an oral arsenic,has become an effective drug in the treatment of myelodysplastic syndromes(MDS)in Xiyuan Hospital,China Academy of Chinese Medical Sciences for many years,and the action mechanism...Qinghuang Powder(QHP),an oral arsenic,has become an effective drug in the treatment of myelodysplastic syndromes(MDS)in Xiyuan Hospital,China Academy of Chinese Medical Sciences for many years,and the action mechanism of the compound or active ingredient AsSof QHP has been elucidated.Considering the relatively safety,chemotherapy-free and convenient oral profile,QHP is widely used in the clinical treatment for MDS patients,especially for elderly patients.In this review,the authors document the efficacy and safety of oral arsenic-containing compound QHP in the treatment of MDS,with a special focus on the association of efficacy of QHP with the cytogenetics,prognostic risk,DNA methylation,gene mutation,blood arsenic concentration,mechanism of action of AsSand the countermeasures against adverse reactions of gastrointestinal tract.展开更多
Objective To investigate expression of Evi 1 and MDS1 Evi 1 genes in myelodysplastic syndromes (MDS) and post MDS acute myeloid leukemia (post MDS AML), and its role in pathogenesis or progression of MDS and pos...Objective To investigate expression of Evi 1 and MDS1 Evi 1 genes in myelodysplastic syndromes (MDS) and post MDS acute myeloid leukemia (post MDS AML), and its role in pathogenesis or progression of MDS and post MDS AML Methods Expression of Evi 1 and MDS1 Evi 1 genes was examined in 31 MDS, 11 post MDS AML, and 34 de novo AML patients by a semi quantitative reverse transcription polymerase chain reaction (RT PCR) Results Evi 1 expression was not detected in bone marrow samples of 8 normal controls, but low MDS1 Evi 1 expression levels (MDS1 Evi 1/GAPDH<0 1) were detected in 3 of the 8 controls Evi 1 RNA was expressed in 1 of 8 RA, 8 of 13 RAEB and 6 of 9 RAEB T patients, and the percentage of Evi 1 expression in RAEB(T) patients was higher than that in RA (P<0 05) MDS1 Evi 1 expression was detected in 5 of 8 RA, 9 of 13 RAEB and 5 of 9 RAEB T patients, and MDS1 Evi 1 expression levels (MDS1 Evi 1/GAPDH>0 1) were markedly higher than those in the controls Evi 1 expression was gradually increased in 4 of 5 RAEB T patients with transformation from MDS to AML The percentages of Evi 1 and MDS1 Evi 1 expression in post MDS AML patients were significantly (P<0 01 and P<0 05 respectively) higher than those in de novo AML The colonies of hematopoietic progenitor cells were decreased in Evi 1 and MDS1 Evi 1 positive MDS patients as compared with those in Evi 1 and MDS1 Evi 1 negative patients Conclusion Abnormal expression of the Evi 1 gene and overexpression of MDS1 Evi 1 gene may play a role in the pathogenesis or progression of MDS and post MDS AML展开更多
BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders i...BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders is well recognized,several cases having been reported.However,inflammatory disorders in patients without MDS have been largely overlooked.Generally,Behçet's disease is the most common type in+8-MDS.However,inflammatory disorders with pulmonary involvement are less frequent,and no effective treatment has been established.CASE SUMMARY A 27-year-old man with recurrent fever,fatigue for>2 mo,and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia.Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing.Epstein–Barr virus and Mycobacterium kansasii were detected.Additionally,chromosomal analysis showed duplications on chromosome 8.Two days later,repeat metagenomic next-generation sequencing was performed with blood culture.Cordyceps portugal,M.kansasii,and Candida portugal were detected,and duplications on chromosome 8 confirmed.Suspecting hematological disease,we aspirated a bone marrow sample from the iliac spine,examination of which showed evidence of infection.We added fluconazole as further antibiotic therapy.Seven days later,the patient’s condition had not improved,prompting addition of methylprednisolone as an anti-inflammatory agent.Fortunately,this treatment was effective and the patient eventually recovered.CONCLUSION Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8.Methylprednisolone may be an effective treatment.展开更多
Background Patients with myelodysplastic syndrome （MDS） display a very diverse pattern. In this study, we investigated prognostic factors and survival rate in adult patients with MDS refractory anaemia （MDS-RA） di...Background Patients with myelodysplastic syndrome （MDS） display a very diverse pattern. In this study, we investigated prognostic factors and survival rate in adult patients with MDS refractory anaemia （MDS-RA） diagnosed according to French-American-British classification and evaluated the International Prognostic Scoring System （tPSS） for Chinese patients. Methods A multi-center study on diagnosis of MDS-RA was conducted to characterize the clinical features of Chinese MDS patients. The morphological criteria for the diagnosis of MDS-RA were first standardized. Clinical data of 307 MDS-RA patients collected from Shanghai, Suzhou and Beijing from 1995 to 2006 were analyzed using Kaplan-Meier curve, log rank and Cox regression model. Results The median age of 307 MDS-RA cases was 52 years. The frequency of 2 or 3 lineage cytopenias was 85.6%. Abnormal karyotype occurred in 35.7% of 235 patients. There were 165 cases （70.2%） in the good IPSS cytogenetic subgroup, 44 cases （18.7%） intermediate and 26 cases （11.1%） poor. IPSS showed 20 （8.5%） categorized as low risk, 195 cases （83.0%） as intermediate-Ⅰ risk and 20 cases （8.5%） as intermediate-Ⅱ risk. The 1-, 2-, 3-, 4- and 5-year survival rates were 90.8%, 85.7%, 82.9%, 74.9% and 71.2% respectively. Fifteen cases （4.9%） transformed to acute myeloid leukaemia （median time 15.9 months, range 3-102 months）. Lower white blood cell count （〈1.5×10^9/L）, platelet count （〈30×10^9/L） and cytogenetic abnormalities were independent prognostic factors by multivariate analysis, but age （〉65 years）, IPSS cytogenetic subgroup and IPSS risk subgroup were not independent prognostic factors associated with survival time. Conclusions Chinese patients were younger, and had lower incidence of cytogenetic abnormalities, more severe cytopenias but a more favourable prognosis than Western patients. The major prognostic factors were lower white blood cell count, lower platelet count and fewer abnormal karyotypes. The international prognostic scoring system risk group was not an independent prognostic factor for Chinese myelodysplastic syndrome patients with refractory anaemia patients.展开更多
基金Supported by a grant from the Tianjin Natural Science Fund (013111111,023609311).
文摘Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). Methods The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor (TNF), CD4^+ and CD8^+ T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed. Results The clone burden of MDS patients was 67.4%±36.2%. MDS clone burden positively correlated with bone marrow blasts (r = 0.483, P<0.05), negatively with hemoglobin level (r=-0.445, P<0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (>50%) and low clone burden (≤50%) groups were 7.78%±5.51% and 3.45%±3.34%, 56.06±14.28 g/L and 76.40±24.44 g/L, (1.82±0.48)×10~ 12 /L and (2.32±0.66)×10~ 12 /L, respectively (all P<0.05). CD4^+ T lymphocytes of MDS patients and normal controls were (0.274±0.719)×10~ 9 /L and (0.455±0.206)×10~ 9 /L, respectively (P<0.05). CD8^+ T lymphocytes of MDS patients and normal controls were (0.240±0.150)×10~ 9 /L and (0.305±0.145)×10~ 9 /L, respectively. The serum level of interleukin-2 of MDS patients (6.29±3.58 ng/mL) was significantly higher than normal control (3.11±1.40 ng/mL, P<0.05). The serum level of TNF of MDS patients and normal control group were 2.42±1.79 ng/mL and 1.68±0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90±0.52) than that in low clone burden patients (0.97±0.44, P<0.05). Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its progression.
基金supported by National Natural Science Foundation of China(No.81170472)Chinese Medical Association Molecular Biology Clinical Application Research Special Funds(No.CAMB042010)Tianjin Application Bases and Advanced Technology Research Program(No.09JCYBJC11200)
文摘Objective This study aims to investigate the expression of delta-like 1 （DLK1） gene in the bone marrow cells of patients with myelodysplastic syndromes （MDS） and to explore its molecular characteristics for the early diagnosis of MDS. Methods The expression of DLK1 mRNA in the bone marrow cells of cases with MDS, acute myeloid leukemia （AML）, and normal control groups were measured by real-time polymerase chain reaction and were analyzed for clinical significance. Results Significantly higher expression of DLK1 mRNA was observed in the bone marrow cells of MDS patients （0.7342±0.3652） compared with the normal control group （0.4801±0.1759） （P〈0.05）. The expression of DLK1 mRNA had a positive correlation with the proportion of bone marrow blasts （r=0.467, P〈0.05）. Moreover, DLK1 mRNA expression was significantly increased as MDS progressed （P〈0.05）. Patients with abnormal karyotypes exhibited significantly higher expression of DLK1 mRNA （0.9007±0.4334） than those with normal karyotypes （0.6411±0.2630） （P〈0.05）. Subsequently, patients with highly expressed DLK1 （≥0.8） presented significantly higher malignant clone burden （0.4134±0.3999） than those with lower DLK1 expression （〈0.8）,（0.1517±0.3109）, （P〈0.05）. Conclusions The DLK1 gene was highly expressed in MDS patients, and was increased as MDS progressed. The expression of DLK1 mRNA was positively correlated with the proportion of the bone marrow blasts. A high expression of DLK1 gene suggested a higher malignant clone burden of MDS.
文摘Sekeres et al. （1） conducted a multicenter randomized, controlled trial to compare whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates to azacitidine in the treatment of myelodysplastic syndromes （MDS）. In that trial, 224 patients with higher-risk MDS and 53 with chronic myelomonocytic leukemia （CMML） were enrolled and randomly assigned to the ＂azacitidine＂ group, ＂azacitidine plus lenalidomide＂ group or ＂azacitidine plus vorinostat＂ group. The researchers found that patients with MDS treated with azacitidine-based combinations had similar response rate to azacitidine monotherapy. Using genomic mutation analysis, they found that the overall response rate to azacitidine-based treatment was higher for patients with mutations in DNMT3A and lower for those with mutations in SRSF2. Whereas in another study, Welch et al. enrolled 26 patients with MDS and 90 with acute myeloid leukemia （AML） who were treated with decitabine, and they found that patients with TP53 mutations had a higher response rate, but not those with DNMT3A mutations （2）. We propose that this big discrepancy in the conclusions between the two studies might have been caused by the presence of many co-interacting factors, e.g. study aims, DNA demethylating agents, treatment protocols, and patient sources.
文摘Myelodysplastic syndrome(MDS)is a malignant clonal disease of human hematopoietic stem cells.In this paper,a case of MDS with fever and rash as the first symptom was reported in our hospital,and the related literature was reviewed and summarized to provide ideas for the diagnosis of MDS.Case summary:The patient,male,62 years old,with systemic rash and fever as the initial symptoms,early multiple bone marrow examination showed no typical abnormalities.With the progress of the disease,bone marrow cytology,flow cytometry,molecular karyotype,chromosomal karyotype,skin biopsy and pathological diagnosis were performed,and the diagnosis was MDS.
文摘Background:Oral administration of indigo naturalis(IN)is used as a complementary and alternative medicine(CAM)regimen for the treatment of myelodysplastic syndromes(MDS).However,its mechanism of action has not been fully elucidated and needs to be further explored.Methods:By searching the traditional Chinese medicine system and analyzing platforms(TCMSP),bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine(BATMAN-TCM),and Swiss Target Prediction network database,the main active components and potential targets of IN were obtained.Based on this,a component-target network was established by Cytoscape 3.6.1 software.Differentially expressed genes(DGEs)in MDS were obtained from three GEO(Gene Expression Omnibus)gene chips.Then,the protein-protein interaction(PPI)network of DGEs was constructed and analyzed by STRING database and Cytoscape 3.6.1 software.In addition,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)biological enrichment analysis were carried out using REVIGO and KEGG Orthology Based Annotation System(KOBAS)on DGEs,respectively.Identification of IN-MDS compound targets was performed by matching potential targets of active components with disease-related targets.The results of KEGG pathway enrichment analysis were combined with compound targets to screen key targets.In the end,molecular docking was performed by SYBYL-X2.1 to verify the key targets.Results:Nine active components of IN and 439 potential targets of IN were identified by analyzing TCMSP,BATMAN-TCM,and Swiss Target Prediction network databases.Three MDS disease-related gene microarray chips were obtained from the GEO databases:GSE4619,GSE19429,and GSE58831.Through this analysis,87 DEGs were finally obtained using the Venn diagram.A PPI network of DEGs was then constructed,in which 18 genes were upregulated and 69 genes were downregulated.After the GO enrichment results were de-redundant,the representative GO terms were obtained by using REVIGO semantic similarity measuremen.The KEGG biological pathway analysis using the KOBAS indicated that the Hippo signaling pathway is important in MDS.The Hippo signaling pathway involves four genes:AREG,LEF1,SMAD7,and TCF4.By matching and mapping DEGs with potential targets,six IN-MDS compound targets were obtained:PDE4B,PLAUR,ELANE,NR3C1,AREG,and LEF1.We found that AREG and LEF1 are consistent with the genes involved in the Hippo signaling pathway.Through molecular docking simulation,we found that the indican binds best to AREG and LEF1.Conclusion:Based on the integrated pharmacology model,the material basis of the efficacy and biological molecular mechanism of IN in the treatment of MDS was systematically studied,which provided a novel indication of the CAM regimen for the improvement of MDS management.
基金supported by grants from the National Natural Science Foundation of China(No.30971286, 30971285,81170472)Chinese Medical Association of Molecular Biology Clinical Application Research Special Funds(No.CAMB042010)+1 种基金The"Eleventh Five-year Plan"National Science and Technology Support Plan(No. 2008BA161B00)Health Industry Research Special Project (No.201002024)
文摘Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells （BMMNC） of patients with myelodysplastic syndrome （MDS） and its clinical significance. Methods The expression of TET2 mRNA and protein in bone marrow mononuclear cells （BMMNC） of 32 patients with MDS and 20 healthy donors was examined by qPCR and Western blot. Results The expression of TET2 mRNA in BMMNC was down-regulated in MDS patients compared with the donor group [（0.41±0.28）% vs. （1.07±0.56）%] （P〈0.001）. Compared with lower expression group （TET2〈0.4） [（6.53±6.17）%], patients with higher expression of TET2 ≥0.4） presented significantly lower proportion of bone marrow blasts [（1.21±1.56）%1 （P〈0.05）. The expression of TET2 mRNA in BMMNC of MDS patients was inversely correlated with malignant clone burden （t=--0.398, P〈0.05） and IPSS r=-0.412, P〈0.05）. The expression of TET2 protein was down-regulated in MDS patients compared with that in the donor group. Conclusions The mRNA and protein expression of TET2 in BMMNC of MDS patients is decreased, which might be useful as an important parameter for the evaluation of MDS clone burden.
文摘Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of MDS: (1) Conventional Cytogenetics (CC) for clonal chromosomal abnormalities; (2) BrdU-Sister Chromatid Differentiation (BrdU-SCD) for cell cycle kinetics; (3) Fluorescence in Situ Hybridization (FISH) for trisomy 8; (4) Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) for N-ras mutation. Results: The diagnosis of forty-three patients was compatible with the FAB criteria for MDS. The other seven cases didn’t meet the FAB criteria, with only one lineage of dyspoiesis or with no obvious dysplastic changes. Among these seven cases, two were morphologically diagnosed with suspicious refractory anemia, one with sideroblastic anemia, one with leukemoid reaction, one with hypercellular anemia and two with chronic aplastic anemia. Clonal analyses of the 7 patients showed that six cases had clonal karyotype abnormalities, four had prolonged cell cycle patterns, four had trisomy 8 of different proportions and one had mutation of the exon 1 of N-RAS. Thus, they were revaluated as MDS patients. Conclusion: The untypical MDS patients with one lineage dyspoiesis or without obvious dysplastic changes can be diagnosed early by combining multiple clonal analysis techniques such as CC, SCD, FISH and PCR-SSCR.
基金a grant from Medical and Health Research Projects in Shandong Province,China(No.2007HW074)
文摘OBJECTIVE Some mtDNA mutations have been detected in patients with myelodysplastic syndromes(MDSs).As the non-coding region of mitochondria,the displacement loop(D-loop) region of mtDNA contains important elements for mtDNA replication and transcription.Variants of the D-loop region were found to be related to the cause of many diseases.The aim of our study was to investigate mutations and single nucleotide polymorphisms in the D-loop region of MDS patients.METHODS The mutations and SNPs in the hypervariable regions of the D-loop were detected by direct sequencing in MDS patients and normal controls.RESULTS Sixty-four SNPs were found in the D-loop region in MDS cases and control group.Among the SNPs,the 16,189 variant(T > C transition) was found to have an increased frequency in the MDS group(P = 0.044).However,no mutations were detected in neither group.CONCLUSION Our data provide evidence for a highly polymorphic D-loop region in patients with MDS,but do not support the presence of mutations in the mitochondrial D-loop region in MDS cases.The mtDNA T16,189C variant,which may be a functional variant,is associated with increased susceptibility to a MDS.
基金Clinical Translational Research of Beijing Municipal Science and Technology Commission,Administrative Commission of Zhongguancun Science Park-funded Project:Study on Mechanisms and Efficacy of Yisui granule Treating Low and Intermediate Risk of Myelodysplastic Syndromes via DNA Demethylation(No.Z211100002921018)National Natural Science Foundation of Chinafunded Projects:Study on Molecular Mechanisms of Yisui granule Treating Myelodysplastic Syndromes via Regulating DNA Methylation(No.81503575)+1 种基金Mechanism Study of Tea Polyphenols activating c GAS-STING Pathway to Inhibit Lung Adenocarcinoma Immune Escape based on Redox Balance(No.82172760)the Golden Bridge Project of Beijing Association for Science and Technology-funded Project:Study on Mechanisms of Yisui granule Treating Low and Intermediate Risk of Myelodysplastic Syndromes via DNA Demethylation(No.ZZ20059)。
文摘OBJECTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MDS).METHODS:Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor potential of YSG and its safety,assess its effect on overall survival(OS),and evaluate whether its mechanism is associated with the demethylation of the secreted frizzled related protein 5(s FRP5)gene and suppressing Wnt/β-catenin pathway.Bisulfite amplicon sequencing was applied to detect the level of methylation of the s FRP5 gene;western blotting,immunofluorescence staining,and real-time Polymerase Chain Reaction were performed to detect DNA methyltransferase 1(DNMT1),s FRP5,and other Wnt/β-catenin pathway-related m RNA and protein expression.RESULTS:The results showed that high-dosage YSG exerted an anti-tumor effect similar to that of decitabine,improved OS,and reduced long-term adverse effects in the long term.Mechanically,YSG reduced the expression of DNMT1 methyltransferase,decreased the methylation,and increased the expression of the Wnt/β-catenin pathway antagonist-s FRP5.Furthermore,components of the Wnt/β-catenin pathway,including Wnt3a,β-catenin,c-Myc,and cyclin D1,were down-regulated in response to YSG,suggesting that YSG could treat MDS by demethylating the s FRP5 gene and suppressing the Wnt/β-catenin pathway.CONCLUSIONS:Our findings demonstrated that YSG could be used alone or in combination with decitabine to improve outcomes in the MDS animal model,providing an alternative solution for treating MDS.
文摘Objective To determine the expression and function of the c-kit receptor in bone marrow mononuclear cells (BMMNC) of patients with myelodysplastic syndromes (MDS). Methods Direct immunofluorescence assay and reverse transcriptase-polymerase chain reaction (RTPCR) were used to detect c-kit protein and c-kit mRNA expressions in the BMMNC of 29 MDS patients and 10 normal controls. Cell culture was used to detect the function of the c-kit receptor. Results c-kit protein expression in the MDS group was significantly higher than that in the control group (8.58％ +5.28％ vs 3.04％ + 1.49％, P＜0.05). c-kit protien expression in the refractory anemia (RA)group was significantly lower than that in the RA with an excess of blasts (RAEB)/RAEB in transformation (RAEB-t) group (5.12％ +2.13％ vs 10.01％ +5.07％, P＜0.05). The rate of c-kit protein expression was 32.43％ in aoute myeloblastic leukemia (AML) cases transformed from MDS (t-AML). c-kit mRNA expression in the MDS group was correlated with c-kit protein expression. Interieukin-3 (IL-3) and erythropoietin (Epo), with or without stem cell factor (SCF), upregulated c-kit protein and its mRNA expression. In the presence of IL-3 and Epo, SCF showed significant stimulating effects on the formation of CFU-GM and BFU-E in semi-solid cultures of normal BMMNC, but had no effects on those of the MDS patients.Conclusion The protein and mRNA expression of the c-kit receptor in the BMMNC of MDS patients were higher than those of normal controls, and the function of this receptor in MDS BMMNC was abnormal. Chin Med J 2001; 114(5) :481-485
文摘Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.Results During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1-23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M 2, M 4, or M 5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD 33 [(49.83±24.50)%], CD 13 [(36.38±33.84)%], monocytic antigen CD 14 [(38.50±24.60)%], and stem cell marker CD 34 [(34.67±30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD 5, CD 7, CD 9, and CD 19, coexisted with myeloid antigens. A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1-28) months, were found in patients with MDS-AML treated by induction chemotherapy.Conclusions MDS has a high risk of developing into AML, either gradually or rapidly. Patients with MDS-AML have specific biological characteristics and a worse prognosis.
文摘The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia(a CML), chronic myelomonocytic leukemia(CMML), juvenile myelomonocytic leukemia(JMML), MDS/MPN-unclassifiable(MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis(RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of nextgeneration platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis,prognostication, and treatment. Future goals of research should include the development of disease-modifying therapies, and further genetic understanding of the category will likely form the foundation of these efforts.
基金Supported by China Academy of Chinese Medicine Scientific Foundation(ZZ13-YQ-010)National Natural Science Foundation of China(No.81603490)State Administration of Traditional Chinese Medicine Foundation(No.JDZX-2015264)。
文摘OBJECTIVE:To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia(MDS-MLD)and arsenic concentration in the peripheral blood of patients.METHODS:In this prospective study,a total of 50 MDS-MLD patients were treated with traditional Chinese drugs containing realgar for 3 months in Xiyuan Hospital from March 2018 to January 2019.Routine blood examination as well as liver and kidney function were monitored before and after treatment.The concentration of arsenic in the peripheral blood was measured using an atomic fluorescence spectrometer after treatment.The correlation between clinical effect and arsenic concentration was analyzed by Spearman’s method.RESULTS:The treatment response rate was 54%.Two patients(4%)achieved complete remission,50%(25 of 50)showed hematologic improvement,and 23 patients had stable disease(23%).No disease progression was observed.Arsenic concentration in the peripheral blood ranged from 14.60 to 85.96μg/L.Clinical efficacy was positively correlated with arsenic concentration(P<0.05).The incidence of mild adverse reactions was 16%.CONCLUSION:A relatively high concentration of arsenic in the peripheral blood may improve the clinical efficacy of realgar in MDS-MLD patients.
文摘Myelodysplastic syndromes （MDS） are a heterogeneous group of clonal disorderscharacterized by ineffective hematopoiesis; they manifest clinically as anemia, neutropenia, and thrombocytopenia.1＇2 Higher risk MDS include patients in the intermediate-2 and high-risk categories of the International Prognostic Scoring System （IPSS）, as well as patients with MDS secondary to radiation or chemical exposure.3 The patients with higher risk MDS have a peculiar propensity to evolve into acute myeloid leukemia （AML）, and have a median survival of 〈12 months.4 Management of higher risk MDS varies from supportive care with transfusions or hematopoietic cytokines to high-intensity3 chemotherapy or hematopoietic stem cell transplantation. The impact of intensive myelosuppressive chemotherapy, similar to AML induction therapy, has been investigated. The results are comparable to the reported outcome of patients with AML, i.e. complete remission （CR） rates of 40%-60% and median overall survival （OS） of 8-12 months,s Thus, innovative approaches are needed for the treatment of higher risk MDS.
文摘OBJECTIVE: To explore the immunophenotype of myeloid cells in myelodysplastic syndyomes (MDS) and its clinical implications. METHODS: A panel of monoclonal antibody was used to detect CD13+, CD33+, CD15+ and CD14+ antigens on the membrane surfaces of myeloid cells in the bone marrow from 51 MDS, 21 aplastic anemia (AA), 21 paroxysmal nocturnal hemoglobinuria (PNH) patients. 10 acute myeloblastic leukemia (AML) patients and 15 normal subjects by immunoenzymatic assay. The morphology and chromosome karyotype of bone marrow cells of MDS patients were also examined. RESULTS: CD14+, CD13+ and CD33+ cells in the bone marrow were more in MDS patients than in normal controls, AA patients and PNH patients. CD15+ cells in the bone marrow were less in MDS patients than in normal controls. CONCLUSIONS: The percentages of CD14+, CD13+ and CD33+ positive cells in the bone marrow of MDS patients were related to the percentage of myeloblasts, the chromosomal aberrations and the response to treatment. It indicated that there is immunophenotypic misexpression of myeloid cells in MDS patients. Immunophenotype analysis of myeloid cells might be useful for the diagnosis and treatment of MDS patients.
文摘DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes(MDS).Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes,inducing gene silencing.Realgar(α-As_(4)S_(4))is a traditional medicine used for the treatment of various diseases in the ancient time.Realgar was reported to have efficacy for acute promyelocytic leukemia(APL).It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS.This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS,as well as the species and metabolisms of arsenic in vivo.
基金Supported by the National Natural Science Foundation of China(No.81673821,81774142)Special Research Foundation of Central Level Public Scientific Research Institutes(No.ZZ10-016)。
文摘Qinghuang Powder(QHP),an oral arsenic,has become an effective drug in the treatment of myelodysplastic syndromes(MDS)in Xiyuan Hospital,China Academy of Chinese Medical Sciences for many years,and the action mechanism of the compound or active ingredient AsSof QHP has been elucidated.Considering the relatively safety,chemotherapy-free and convenient oral profile,QHP is widely used in the clinical treatment for MDS patients,especially for elderly patients.In this review,the authors document the efficacy and safety of oral arsenic-containing compound QHP in the treatment of MDS,with a special focus on the association of efficacy of QHP with the cytogenetics,prognostic risk,DNA methylation,gene mutation,blood arsenic concentration,mechanism of action of AsSand the countermeasures against adverse reactions of gastrointestinal tract.
文摘Objective To investigate expression of Evi 1 and MDS1 Evi 1 genes in myelodysplastic syndromes (MDS) and post MDS acute myeloid leukemia (post MDS AML), and its role in pathogenesis or progression of MDS and post MDS AML Methods Expression of Evi 1 and MDS1 Evi 1 genes was examined in 31 MDS, 11 post MDS AML, and 34 de novo AML patients by a semi quantitative reverse transcription polymerase chain reaction (RT PCR) Results Evi 1 expression was not detected in bone marrow samples of 8 normal controls, but low MDS1 Evi 1 expression levels (MDS1 Evi 1/GAPDH<0 1) were detected in 3 of the 8 controls Evi 1 RNA was expressed in 1 of 8 RA, 8 of 13 RAEB and 6 of 9 RAEB T patients, and the percentage of Evi 1 expression in RAEB(T) patients was higher than that in RA (P<0 05) MDS1 Evi 1 expression was detected in 5 of 8 RA, 9 of 13 RAEB and 5 of 9 RAEB T patients, and MDS1 Evi 1 expression levels (MDS1 Evi 1/GAPDH>0 1) were markedly higher than those in the controls Evi 1 expression was gradually increased in 4 of 5 RAEB T patients with transformation from MDS to AML The percentages of Evi 1 and MDS1 Evi 1 expression in post MDS AML patients were significantly (P<0 01 and P<0 05 respectively) higher than those in de novo AML The colonies of hematopoietic progenitor cells were decreased in Evi 1 and MDS1 Evi 1 positive MDS patients as compared with those in Evi 1 and MDS1 Evi 1 negative patients Conclusion Abnormal expression of the Evi 1 gene and overexpression of MDS1 Evi 1 gene may play a role in the pathogenesis or progression of MDS and post MDS AML
基金Major Project of Jinhua Science and Technology Bureaun,No.2021-3-025。
文摘BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders is well recognized,several cases having been reported.However,inflammatory disorders in patients without MDS have been largely overlooked.Generally,Behçet's disease is the most common type in+8-MDS.However,inflammatory disorders with pulmonary involvement are less frequent,and no effective treatment has been established.CASE SUMMARY A 27-year-old man with recurrent fever,fatigue for>2 mo,and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia.Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing.Epstein–Barr virus and Mycobacterium kansasii were detected.Additionally,chromosomal analysis showed duplications on chromosome 8.Two days later,repeat metagenomic next-generation sequencing was performed with blood culture.Cordyceps portugal,M.kansasii,and Candida portugal were detected,and duplications on chromosome 8 confirmed.Suspecting hematological disease,we aspirated a bone marrow sample from the iliac spine,examination of which showed evidence of infection.We added fluconazole as further antibiotic therapy.Seven days later,the patient’s condition had not improved,prompting addition of methylprednisolone as an anti-inflammatory agent.Fortunately,this treatment was effective and the patient eventually recovered.CONCLUSION Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8.Methylprednisolone may be an effective treatment.
文摘Background Patients with myelodysplastic syndrome （MDS） display a very diverse pattern. In this study, we investigated prognostic factors and survival rate in adult patients with MDS refractory anaemia （MDS-RA） diagnosed according to French-American-British classification and evaluated the International Prognostic Scoring System （tPSS） for Chinese patients. Methods A multi-center study on diagnosis of MDS-RA was conducted to characterize the clinical features of Chinese MDS patients. The morphological criteria for the diagnosis of MDS-RA were first standardized. Clinical data of 307 MDS-RA patients collected from Shanghai, Suzhou and Beijing from 1995 to 2006 were analyzed using Kaplan-Meier curve, log rank and Cox regression model. Results The median age of 307 MDS-RA cases was 52 years. The frequency of 2 or 3 lineage cytopenias was 85.6%. Abnormal karyotype occurred in 35.7% of 235 patients. There were 165 cases （70.2%） in the good IPSS cytogenetic subgroup, 44 cases （18.7%） intermediate and 26 cases （11.1%） poor. IPSS showed 20 （8.5%） categorized as low risk, 195 cases （83.0%） as intermediate-Ⅰ risk and 20 cases （8.5%） as intermediate-Ⅱ risk. The 1-, 2-, 3-, 4- and 5-year survival rates were 90.8%, 85.7%, 82.9%, 74.9% and 71.2% respectively. Fifteen cases （4.9%） transformed to acute myeloid leukaemia （median time 15.9 months, range 3-102 months）. Lower white blood cell count （〈1.5×10^9/L）, platelet count （〈30×10^9/L） and cytogenetic abnormalities were independent prognostic factors by multivariate analysis, but age （〉65 years）, IPSS cytogenetic subgroup and IPSS risk subgroup were not independent prognostic factors associated with survival time. Conclusions Chinese patients were younger, and had lower incidence of cytogenetic abnormalities, more severe cytopenias but a more favourable prognosis than Western patients. The major prognostic factors were lower white blood cell count, lower platelet count and fewer abnormal karyotypes. The international prognostic scoring system risk group was not an independent prognostic factor for Chinese myelodysplastic syndrome patients with refractory anaemia patients.
