Acute myeloid leukemia(AML)is a malignant hematological tumor with disordered oncogenes/tumor suppressor genes and limited treatments.The potent anti-cancer effects of bromodomain and extra-terminal domain(BET)inhibit...Acute myeloid leukemia(AML)is a malignant hematological tumor with disordered oncogenes/tumor suppressor genes and limited treatments.The potent anti-cancer effects of bromodomain and extra-terminal domain(BET)inhibitors,targeting the key component of super enhancers,in early clinical trials on AML patients,implies the critical role of super enhancers in AML.Here,we review the concept and characteristic of super enhancer,and then summarize the current researches about super enhancers in AML pathogenesis,diagnosis and classification,followed by illustrate the potential super enhancer-related targets and drugs,and propose the future directions of super enhancers in AML.This information provides integrated insight into the roles of super enhancers in this disease.展开更多
Electron beam（EB） irradiation experiments on Au/ITO and ITO/Au/ITO multilayer thin films are reported.The structure and the optical-electrical properties of the samples were investigated by X-ray diffraction,atomic ...Electron beam（EB） irradiation experiments on Au/ITO and ITO/Au/ITO multilayer thin films are reported.The structure and the optical-electrical properties of the samples were investigated by X-ray diffraction,atomic force microscopy, four-point probe resistivity measurement system, and UV–vis-NIR double beam spectrometer, respectively. Those results show that the EB irradiation has the effects of improving the crystalline of samples, widening the optical band gap of both thin films, reducing the sheet resistance,and improving the transmittance of samples.展开更多
T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell progenitors.The development of targeted therapeutic regimens is impeded by poo...T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell progenitors.The development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this disease.In this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this disease.This multi-omics integration helped identify 29 potential pathological genes for T-ALL.These genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling pathway.Of these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in T-ALL.The TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive stage.CDK6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation stages.Furthermore,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in T-ALL.Collectively,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.展开更多
基金This work was partially supported by the Natural Science Foundation of China(No.82070167,81870126,and 81802803).
文摘Acute myeloid leukemia(AML)is a malignant hematological tumor with disordered oncogenes/tumor suppressor genes and limited treatments.The potent anti-cancer effects of bromodomain and extra-terminal domain(BET)inhibitors,targeting the key component of super enhancers,in early clinical trials on AML patients,implies the critical role of super enhancers in AML.Here,we review the concept and characteristic of super enhancer,and then summarize the current researches about super enhancers in AML pathogenesis,diagnosis and classification,followed by illustrate the potential super enhancer-related targets and drugs,and propose the future directions of super enhancers in AML.This information provides integrated insight into the roles of super enhancers in this disease.
基金supported financially by the National Key Research and Development Program of China (No. 2016YFB1102303)the National Basic Research Program of China (973 Program) (No. 2015CB352001)the National Natural Science Foundation of China(No. 61378060)
文摘Electron beam（EB） irradiation experiments on Au/ITO and ITO/Au/ITO multilayer thin films are reported.The structure and the optical-electrical properties of the samples were investigated by X-ray diffraction,atomic force microscopy, four-point probe resistivity measurement system, and UV–vis-NIR double beam spectrometer, respectively. Those results show that the EB irradiation has the effects of improving the crystalline of samples, widening the optical band gap of both thin films, reducing the sheet resistance,and improving the transmittance of samples.
基金the National Natural Science Foundation of China(No.82070167,81870126,81900190,81802803)The Chongqing Science and Technology Bureau Major Project,Chongqing,China(No.cstc2020jcyjmsxmX0782).
文摘T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell progenitors.The development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this disease.In this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this disease.This multi-omics integration helped identify 29 potential pathological genes for T-ALL.These genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling pathway.Of these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in T-ALL.The TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive stage.CDK6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation stages.Furthermore,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in T-ALL.Collectively,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.
