MicroRNA"s in the Treatment of AML

治疗 AML 中的 MicroRNA

• 批准号: 7270266
• 负责人: CARLO M CROCE
• 金额: $ 29.09万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270266
• 关键词: 11q23; 13q14; Acute; Acute Myelocytic Leukemia; Acute Promyelocytic Leukemia; Algorithms; Apoptosis; Apoptotic; B-Cell Lymphomas; B-Lymphocytes; BCL-2 Protein; BCL2 gene; Biological Assay; Bone Marrow Transplantation; Cells; Cessation of life; Chromosomal translocation; Chromosome Mapping; Chromosome abnormality; Chromosomes; Chromosomes, Human, Pair 5; Chronic Lymphocytic Leukemia; Clinical; Collaborations; Cytogenetics; Data; Data Set; Databases; Detection; Development; Diagnosis; Disease; Disease remission; Doctor of Medicine; Doctor of Philosophy; Down-Regulation; Event; Gene Chips; Gene Expression; Gene Fusion; Genes; Genomics; Germ-Line Mutation; Grant; Hematopoietic; Hematopoietic Neoplasms; Human; Individual; Indolent; Lead; Leukemic Cell; Luciferases; MCL1 gene; MLL gene; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Maps; Measures; Messenger RNA; Methods; MicroRNAs; Molecular Profiling; Mutation; Newly Diagnosed; Numbers; Oncogenes; Paper; Pathogenesis; Pathway interactions; Patients; Pattern; Phosphoproteins; Play; Process; Protein Overexpression; Proteins; Proteomics; Reaction; Regulation; Relapse; Reporter; Research Personnel; Resistance; Risk; Role; Sampling; Societies; Syndrome; Telephone; Tissues; Transgenic Mice; Translations; Tumor Suppressor Proteins; base; cancer cell; chemotherapy; chromosome 5q loss; fusion gene; human MCL1 protein; in vivo; innovation; interest; leukemia; leukemia/lymphoma; leukemogenesis; novel; outcome forecast; prognostic; programs; protein expression; response; t(8; 21)(q22; q22); tool; transcriptomics

MicroRNAs for the diagnosis, prognosis and treatment of AMLs We have discovered alterations of microRNA genes in human leukemias, have discovered that a large fraction of microRNA genes are in chromosomal regions involved in genomic alterations in cancers, have discovered somatic and germ line mutations of microRNA genes in leukemias, and have developed a microRNA platform to investigate the global expression of microRNA genes in normal and leukemic tissues. In addition, we have discovered that miR15/miR16 cause apoptosis by targeting BCL2 and that miR221 and 222 targetKIT. In this proposal we apply our platform to investigate the role of microRNA genes in the pathogenesis and progression of AMLs and to develop better prognostic indicators of these diseases. In addition, the identification of altered microRNA genes involved in the pathogenesis of AMLs could provide new, important targets for the development of novel therapies based on microRNAs or their antisense, depending on whether the pathogenetic microRNAs function as suppressors or oncogenes respectively. We have already made significant progress and have identified microRNAs that may play an important role in AML. This project is highly integrated with the other projects of this program and provides them with microRNA targets involved in the apoptotic process.

MicroRNA 用于 AML 的诊断、预后和治疗 我们发现了人类白血病中 microRNA 基因的改变，发现了很大一部分 部分 microRNA 基因位于参与癌症基因组改变的染色体区域， 发现了白血病中 microRNA 基因的体细胞和种系突变，并开发了一种 microRNA 平台用于研究正常和白血病组织中 microRNA 基因的整体表达。 此外，我们还发现miR15/miR16通过靶向BCL2引起细胞凋亡，并且miR221和 222 目标套件。 在本提案中，我们应用我们的平台来研究 microRNA 基因在发病机制中的作用和 AML 的进展并开发这些疾病的更好的预后指标。此外， 鉴定参与 AML 发病机制的改变的 microRNA 基因可以提供新的、重要的 开发基于 microRNA 或其反义的新疗法的目标，具体取决于 致病性 microRNA 是否分别充当抑制基因或癌基因。我们已经 取得了重大进展，并确定了可能在 AML 中发挥重要作用的 microRNA。 该项目与该计划的其他项目高度集成，并为他们提供 microRNA 参与细胞凋亡过程的靶标。