Specialized Program Of Research Excellence (SPORE) in Leukemia

描述(由申请者提供)：华盛顿大学白血病孢子项目是一个高度动态的转化型癌症研究项目，专门关注白血病和骨髓增生异常综合征(MDS)。我们组建了一支优秀的研究人员团队，他们在基础和临床白血病研究方面具有互补的专业知识。在这个孢子中，我们利用癌症基因组学、免疫学和造血学方面的专业知识来开发白血病的创新翻译研究。我们的长期目标是为白血病和MDS开发新的生物标记物和治疗方法，并招募和促进创新的转化性白血病研究。为实现这些目标，提出了以下具体目标。 目的1.利用肿瘤基因组学的最新进展，开发白血病和MDS的新生物标志物和治疗方法。华盛顿大学一直处于急性髓系白血病和MDS基因组研究的前沿。通过对原发急性髓系白血病(AML)和骨髓增生异常综合征(MDS)基因组测序，我们发现了几个与DNA甲基化(DNMT3A和IDH1)和RNA剪接(U2AF1)相关的新的重复突变基因。这项基础研究促成了以下两个翻译孢子项目的发展。 项目1.地西他滨反应的分子决定因素 项目3.开发治疗骨髓增生异常综合征和急性髓系白血病的RNA剪接调节剂。 目的2.利用当地在免疫学和造血学方面的专业知识，开发白血病和骨髓增生异常综合征的新疗法。在基础免疫学和造血研究方面的机构专业知识导致了白血病两个创新翻译项目的发展。 项目2：针对急性淋巴细胞性白血病的骨髓微环境。 项目4.移植物抗宿主病和移植物抗白血病的表观遗传调控。 目的3.加强支持转化性白血病研究的基础设施。该孢子将支持以下共享的研究资源：1)核心A.生物素加工；2)核心 B.生物统计学；以及3)核心C.管理。 目的4.招募和培训翻译研究方面的新研究者。 目的5.促进孢子间的协作。

DESCRIPTION (provided by applicant): The Washington University SPORE in Leukemia is a highly dynamic translational cancer research program that focuses specifically on leukemias and myelodysplastic syndromes (MDS). We have assembled an outstanding group of investigators with complementary expertise in basic and clinical leukemia research. In this SPORE, we leverage expertise in cancer genomics, immunology, and hematopoiesis to develop innovative translational research in leukemia. Our long term goal is to develop novel biomarkers and treatments for leukemias and MDS and to recruit and promote innovative translational leukemia research. To achieve these goals, the following specific aims are proposed. Aim 1. To exploit recent advances in cancer genomics to develop novel biomarkers and treatments for leukemias and MDS. Washington University has been at the forefront of genomic studies in AML and MDS. Through sequencing of primary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) genomes, we identified several novel recurring mutations of genes involved in DNA methylation (DNMT3A and IDH1) and RNA splicing (U2AF1). This basic research has led to the development of the following two translational SPORE projects. Project 1. Molecular determinants of decitabine responsiveness Project 3. Development of RNA splicing modulators for myelodysplastic syndromes and AML. Aim 2. To leverage local expertise in immunology and hematopoiesis to develop novel treatments for leukemias and myelodvsplastic syndromes. Institutional expertise in basic immunology and hematopoiesis research has led to the development of two innovative translational projects in leukemia. Project 2. Targeting the bone marrow microenvironment in acute lymphocytic leukemia. Project 4. Epigenetic modulation of graft versus host disease and graft versus leukemia. Aim 3. To enhance the infrastructure that supports translational leukemia research. This SPORE will support the following Shared Research Resources: 1) Core A. Biospecimen Processing; 2) Core B. Biostatistics; and 3) Core C. Administration. Aim 4. To recruit and train new investigators in translational research. Aim 5. To facilitate inter-SPORE collaboration.