OriginalTranslation t(8;21)(q22;q22)acute myeloid leukemia(AML)is a highly heterogeneous hematological malignancy with a high relapse rate in China.Two leukemic myeloblast populations(CD34^(+)CD117^(dim) and CD34^(+)C...OriginalTranslation t(8;21)(q22;q22)acute myeloid leukemia(AML)is a highly heterogeneous hematological malignancy with a high relapse rate in China.Two leukemic myeloblast populations(CD34^(+)CD117^(dim) and CD34^(+)CD117^(bri))were previously identified in t(8;21)AML,and CD34^(+)CD117^(dim) cell proportion was determined as an independent factor for this disease outcome.Here,we examined the impact of CD34^(+)CD117^(dim)/CD34^(+)CD117^(bri) myeloblast-associated gene expression on t(8;21)AML clinical prognosis.In this study,85 patients with t(8;21)AML were enrolled.The mRNA expression levels of CD34^(+)CD117^(dim)-associated genes(LGALS1,EMP3,and CRIP1)and CD34^(+)CD117^(bri)-associated genes(TRH,PLAC8,and IGLL1)were measured using quantitative reverse transcription PCR.Associations between gene expression and clinical outcomes were determined using Cox regression models.Results showed that patients with high LGALS1,EMP3,or CRIP1 expression had significantly inferior overall survival(OS),whereas those with high TRH or PLAC8 expression showed relatively favorable prognosis.Univariate analysis revealed that CD19,CD34^(+)CD117^(dim) proportion,KIT mutation,minimal residual disease(MRD),and expression levels of LGALS1,EMP3,CRIP1,TRH and PLAC8 were associated with OS.Multivariate analysis indicated that KIT mutation,MRD and CRIP1 and TRH expression levels were independent prognostic variables for OS.Identifying the clinical relevance of CD34^(+)CD117^(dim)/CD34^(+)CD117^(bri) myeloblast-associated gene expression may provide new clinically prognostic markers for t(8;21)AML.展开更多
Hematopoietic stem cells(HSCs)are an attractive target for gene therapy,especially for inherited blood diseases.Moreover,recombinant lentiviral vectors are considered to be prospective in HSCs gene therapy for the hig...Hematopoietic stem cells(HSCs)are an attractive target for gene therapy,especially for inherited blood diseases.Moreover,recombinant lentiviral vectors are considered to be prospective in HSCs gene therapy for the high efficiency of infection.In this study,murine mononuclear cells(MNCs)were isolated from bone marrow and cultured in suspension,and then Lin−CD117+HSCs were isolated by immunomagnetic beads.During culturing,cells and colonies increased in HSCs supplied with cytokines while no change was observed in the control group without cytokines.FUXW recombinant lentiviral vectors were produced by calcium phosphate-mediated transient cotransfection infected MNCs from ICR and C57 mice.The hFIX expressions were 41.7±4.2 ng/mL and 34.5±6.6 ng/mL in supernatant on 7d.The hFIX expressions of HSCs infected by FUXW recombinant lentiviral vectors were 46.6±5.7 ng/mL(with cytokines)and 33.3±4.8 ng/mL(without cytokines)in supernatant on 7d.Results indicate that recombinant lentiviral vectors can infect murine MNCs and Lin−CD117+HSCs efficiently,and expression of the transgene can be improved when supplied with cytokines.展开更多
基金This study was supported by the National Natural Science Foundation of China(No.81800147)Shanghai Sailing Program(No.18YF1413700)+2 种基金the National Key Research and Development Plan of China(No.2018YFA0107800)the National Natural Science Foundation of China(No.81890994)the National Key Research and Development Plan of China(No.2017YFA0506200)。
文摘OriginalTranslation t(8;21)(q22;q22)acute myeloid leukemia(AML)is a highly heterogeneous hematological malignancy with a high relapse rate in China.Two leukemic myeloblast populations(CD34^(+)CD117^(dim) and CD34^(+)CD117^(bri))were previously identified in t(8;21)AML,and CD34^(+)CD117^(dim) cell proportion was determined as an independent factor for this disease outcome.Here,we examined the impact of CD34^(+)CD117^(dim)/CD34^(+)CD117^(bri) myeloblast-associated gene expression on t(8;21)AML clinical prognosis.In this study,85 patients with t(8;21)AML were enrolled.The mRNA expression levels of CD34^(+)CD117^(dim)-associated genes(LGALS1,EMP3,and CRIP1)and CD34^(+)CD117^(bri)-associated genes(TRH,PLAC8,and IGLL1)were measured using quantitative reverse transcription PCR.Associations between gene expression and clinical outcomes were determined using Cox regression models.Results showed that patients with high LGALS1,EMP3,or CRIP1 expression had significantly inferior overall survival(OS),whereas those with high TRH or PLAC8 expression showed relatively favorable prognosis.Univariate analysis revealed that CD19,CD34^(+)CD117^(dim) proportion,KIT mutation,minimal residual disease(MRD),and expression levels of LGALS1,EMP3,CRIP1,TRH and PLAC8 were associated with OS.Multivariate analysis indicated that KIT mutation,MRD and CRIP1 and TRH expression levels were independent prognostic variables for OS.Identifying the clinical relevance of CD34^(+)CD117^(dim)/CD34^(+)CD117^(bri) myeloblast-associated gene expression may provide new clinically prognostic markers for t(8;21)AML.
基金supported by the National Natural Science Foundation of China (No.30100102).
文摘Hematopoietic stem cells(HSCs)are an attractive target for gene therapy,especially for inherited blood diseases.Moreover,recombinant lentiviral vectors are considered to be prospective in HSCs gene therapy for the high efficiency of infection.In this study,murine mononuclear cells(MNCs)were isolated from bone marrow and cultured in suspension,and then Lin−CD117+HSCs were isolated by immunomagnetic beads.During culturing,cells and colonies increased in HSCs supplied with cytokines while no change was observed in the control group without cytokines.FUXW recombinant lentiviral vectors were produced by calcium phosphate-mediated transient cotransfection infected MNCs from ICR and C57 mice.The hFIX expressions were 41.7±4.2 ng/mL and 34.5±6.6 ng/mL in supernatant on 7d.The hFIX expressions of HSCs infected by FUXW recombinant lentiviral vectors were 46.6±5.7 ng/mL(with cytokines)and 33.3±4.8 ng/mL(without cytokines)in supernatant on 7d.Results indicate that recombinant lentiviral vectors can infect murine MNCs and Lin−CD117+HSCs efficiently,and expression of the transgene can be improved when supplied with cytokines.
