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慢性粒细胞白血病耐伊马替尼细胞系的转录组分析
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作者 韩笑 邓之奎 +2 位作者 张成婉 于亮 刘小宁 《中国实验血液学杂志》 CAS CSCD 北大核心 2021年第6期1714-1718,共5页
目的:探讨调控慢性粒细胞白血病(CML)耐伊马替尼的基因,以提高CML耐伊马替尼患者的治疗效果。方法:选取伊马替尼敏感细胞系K562和耐药细胞系K562/G01,采用RNA-seq方法获得对应细胞的转录组,并进行标准生物信息学分析。结果:相较于K562细... 目的:探讨调控慢性粒细胞白血病(CML)耐伊马替尼的基因,以提高CML耐伊马替尼患者的治疗效果。方法:选取伊马替尼敏感细胞系K562和耐药细胞系K562/G01,采用RNA-seq方法获得对应细胞的转录组,并进行标准生物信息学分析。结果:相较于K562细胞,耐伊马替尼细胞K562/G01转录组中共有464个表达显著变化的基因,其中163个基因表达上调,301个基因表达下调。GO功能注释分析和KEGG通路的富集分析结果显示,差异基因主要集中在氧化磷酸化、蛋白细胞器定位、核糖核蛋白复合体的生物发生等生物学过程。GSEA基因富集分析表明,有5个基因集在K562/G01中被显著的上调,如TGF-beta信号通路、mTOR信号通路、慢性粒细胞白血病相关信号通路等。结论:CML细胞伊马替尼耐药与细胞中氧化磷酸化过程有关,在耐药过程中TGF-beta信号通路、mTOR信号通路发生显著上调。 展开更多
关键词 慢性粒细胞白血病 伊马替尼耐药 转录组
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miR-155-5p对急性髓系白血病细胞凋亡的影响及可能机制 被引量:3
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作者 邓之奎 朱伟 《江苏大学学报(医学版)》 CAS 2020年第2期138-143,共6页
目的:探讨miR-155-5p对急性髓系白血病(acute myeloid leukemia,AML)细胞凋亡的影响及可能机制。方法:收集43例AML患者和21例缺铁性贫血患者的骨髓单个核细胞(bone marrow mononuclear cells,BMMNC),qRT-PCR法检测两组细胞miR-155-5p和B... 目的:探讨miR-155-5p对急性髓系白血病(acute myeloid leukemia,AML)细胞凋亡的影响及可能机制。方法:收集43例AML患者和21例缺铁性贫血患者的骨髓单个核细胞(bone marrow mononuclear cells,BMMNC),qRT-PCR法检测两组细胞miR-155-5p和Bcl-2 mRNA表达水平。AML细胞转染miR-155-5p类似物或抑制剂后,CCK-8法检测经不同浓度阿糖胞苷作用后AML细胞的活性,流式细胞术检测经阿糖胞苷(0.16μg/mL)作用后AML细胞的凋亡情况。通过qRT-PCR和蛋白质印迹法分别检测AML细胞转染miR-155-5p抑制剂后NF-κB、Bcl-2的mRNA和蛋白表达水平。结果:AML患者较缺铁性贫血患者BMMNC的miR-155-5p(t=4.688,P=0.002)和Bcl-2 mRNA(t=4.066,P=0.014)的表达水平明显升高。CCK-8和流式细胞术检测结果显示,转染miR-155-5p类似物的AML细胞经阿糖胞苷处理后细胞活性增高,凋亡明显减少;相反,转染miR-155-5p抑制剂组细胞活性降低,凋亡明显增多(P均<0.01)。qRT-PCR和蛋白质印迹结果显示,转染miR-155-5p抑制剂后AML细胞NF-κB、Bcl-2表达水平降低。结论:miR-155-5p可能通过上调NF-κB、Bcl-2的表达抑制AML细胞凋亡。 展开更多
关键词 急性髓系白血病 miR-155-5p 核因子ΚB BCL-2 凋亡
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新免疫标志组合在多参数流式细胞术检测多发性骨髓瘤微小残留病中的应用 被引量:2
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作者 左晓佳 冯尽意 +3 位作者 叶丽霖 邢苗 邓之奎 刘定胜 《同济大学学报(医学版)》 CAS 2020年第6期722-728,共7页
目的多参数流式细胞术(multiparameter flow cytometry,MFC)检测多发性骨髓瘤(multiple myeloma,MM)微小残留病(minimal residual disease,MRD)细胞和非MM浆细胞两者免疫标志表达的区别。方法2012年4月至2020年4月淮安市第一人民医院和... 目的多参数流式细胞术(multiparameter flow cytometry,MFC)检测多发性骨髓瘤(multiple myeloma,MM)微小残留病(minimal residual disease,MRD)细胞和非MM浆细胞两者免疫标志表达的区别。方法2012年4月至2020年4月淮安市第一人民医院和上海健康医学院附属周浦医院收治的44例具有MRD的MM患者和43例非MM患者分别为研究组和对照组,应用10色流式细胞仪检测浆细胞CD45、CD19、CD56、CD28、CD117、CD20以及CD44、CD49d和CD184表达情况。结果与非MM浆细胞高表达不同,MM的MRD细胞中CD44为低表达,两类细胞的表达差异有统计学意义(P=0.007),CD44可能是MM检测MRD免疫标志之一;CD49d和CD184广泛存在于MM的MRD细胞和非MM浆细胞中,但缺乏特异性,不能作为MM特异性免疫标志;利用CD45、CD19、CD56、CD28、CD117、CD20和CD44的界值判断免疫标志的异常个数,MM的MRD细胞中位异常免疫标志数为4(2~6)个,而非MM浆细胞为0(0~2)个。结论通过MFC检测新的免疫标志组合CD45、CD19、CD56、CD28、CD117、CD20和CD44可以有效的鉴别出MM的MRD细胞。 展开更多
关键词 浆细胞 多发性骨髓瘤 多参数流式细胞术 微小残留病
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Prolonged chronic phase in chronic myelogenous leukemia after homoharringtonine therapy 被引量:3
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作者 LI Yu-feng deng zhi-kui +4 位作者 XUAN Heng-bao ZHU Jia-bin DING Bang-he LIU Xiao-ning CHEN Bao-an 《Chinese Medical Journal》 SCIE CAS CSCD 2009年第12期1413-1417,共5页
Background Homoharringtonine (HHT) is effective in treating late stage chronic myelogenous leukaemia (CML), but little is known about long term maintenance during complete cytogenetic response. Long term efficacy ... Background Homoharringtonine (HHT) is effective in treating late stage chronic myelogenous leukaemia (CML), but little is known about long term maintenance during complete cytogenetic response. Long term efficacy and toxicity profiles of low dose HHT were evaluated in this study. Methods One hundred and six patients with CML received 1.5 mg/m^2 of HHT alone by continuous daily infusion for seven to nine days every four weeks. Of 79 patients in the control group, 31 were treated with interferon α (IFN-α) and 48 with hydroxycarbamide. For 17 patients who failed to achieve cytogenetic response within 12 months' treatment of IFN-α, HHT was administered. Quantitative RT-PCR was used to detect the BCR-ABL mRNA expression in 36 Philadelphia positive CML patients enrolled after 2007. Haematological and cytogenetic responses were evaluated in all patients at the 12th month of follow-up. Long term efficacy was assessed in a follow-up with a median time of 54 months (12 months-98 months). Results After 12 months of therapy, cytogenetic response rate of the HHT, IFN-α and hydroxycarbamide groups were 39/106, 14/31 and 3/48, and corresponding molecular cytogenetic response rates 6/18, 3/8 and 0. Of the 17 patients who received HHT as salvage treatment, 6 achieved cytogenetic response (3 major). At the 48 months' follow-up, cytogenetic response was maintained in 32/39 patients treated with HHT. Patients who had cytogenetic response in HHT group or treated with IFN-α also showed longer median chronic durations, which were 45 months (12 months-98 months) and 49 months (12 months-92 months) respectively, indicating a longer survival time. Conclusions Low dose HHT alone showed considerable short term and long term efficacy in the treatment of late stage CML. It may also be a good choice for patients who have failed imatinib, IFN-α treatment or haematopoietic stem cell transplantation or cannot afford these treatments. 展开更多
关键词 HOMOHARRINGTONINE chronic myelogenous leukaemia long term efficacy
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