急性早幼粒细胞白血病microRNA分析及新型纳米探针的研究

MicroRNAs (miRNAs) play key regulatory roles in a diverse range of biological processes. Alteration of miRNA expression pattern is associated with various diseases,especially with cancers.Acute promyelocytic leukemia (APL) is a form of acute myeloid leukemia, (AML)-M3 subtype. It is considered as the most malignant form of acute leukemia showing a severe bleeding tendency and a short time fatal course. This proposal employs next generation high throughput sequencing and microarray technologies, develops various multifunctional nanoprobes with unique optical or electrochemical properties by controllable synthesis of nanoparties and subsequent rational design.A series ofeffective detection strategiesareproposed to analyze the APL-related miRNA in circular blood and cancer intracellular processes by using various electrochemical, fluorescent spectroscopic, confocal cell imaging detection means. Furthermore, intensive study will be focused on miRNA profile in acute promyelocytic leukemia cell lines, and the clinical samples including the serum and tissue of the As2O3-APL-patient with control. The principle and mechanism of miRNA in the As2O3-related therapy to APL-patient will be explored. By the combination of novel nanotechnology and the result of the principle and mechanism of miRNA in the As2O3-related therapy, novel functional nanodrug will be designed. Therefore, the proposed work possesses promising application in development of novel useful detection strategies for diagnostic and prognostic APL cancer markers and exploitation of novel APL cancer drugs.

MicroRNA（miRNA）作为一种调控分子，对生物体中的一系列生命过程起重要作用，其表达模式改变与人类的很多疾病，尤其癌症，密切相关。急性早幼粒细胞白血病（APL）,是急性非淋巴细胞白血病的M3型,发病急、较凶险。本项目将高通量测序技术与基因芯片技术结合，设计性能优良的光学和电化学纳米探针，利用多种光学、电化学及细胞成像检测手段，原创性地提出一系列用于APL病人外周血和肿瘤细胞内miRNA 检测的新方法，并以急性早幼粒细胞、临床急性早幼粒细胞白血病患者血液和组织中miRNA图谱为研究对象，揭示As2O3药物治疗前后急性早幼粒细胞中miRNA的变化规律，探索与之相关的As2O3药物的作用机制。进一步基于As2O3药物的作用机制及miRNA特异性表达的研究，构建有效的纳米药物。本项目将为寻找APL的新的标记物，新型药物设计和开发提供新方法与新技术，对于APL的诊断和治疗具有重要意义。

MicroRNA（miRNA）作为一种调控分子，在生物体中一系列生命过程起着重要作用，其表达模式改变与人类的很多疾病，尤其癌症，密切相关。急性早幼粒细胞白血病（acute promyelocytic leukemia, APL）是白血病的急性非淋巴细胞白血病的M3型，在临床上较为常见，发病急，较凶险，早期死亡率高。本项目借助高通量测序技术，结合基因芯片技术，以急性早幼粒细胞、临床急性早幼粒细胞白血病患者血液、组织中miRNA图谱为研究对象，揭示As2O3药物治疗前后的急性早幼粒细胞中miRNA的变化规律，探索急性早幼粒细胞白血病中miRNA的特异性表达及与之相关的As2O3药物的作用机制。基于As2O3药物的作用机制及miRNA特异性表达的研究，并结合纳米探针优良的光学和电化学性能，利用多种光学、电化学及细胞成像技术，原创性地提出一系列用于APL病人外周血和肿瘤细胞内miRNA 检测的新方法，构建有效的纳米药物。本项目将为寻找APL的新的标记物，新型药物设计和开发提供新方法与新技术，对于APL的诊断和治疗具有重要意义。