Specialized Program Of Research Excellence (SPORE) in Leukemia

描述（由申请人提供）：华盛顿大学的孢子在白血病是一个高度动态的转化癌症研究计划，特别侧重于白血病和骨髓增生异常综合征（MDS）。我们已经组建了一个优秀的研究小组，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SPORE中，我们利用癌症基因组学，免疫学和造血方面的专业知识来开发白血病的创新转化研究。我们的长期目标是为白血病和MDS开发新的生物标志物和治疗方法，并招募和促进创新的转化白血病研究。为实现这些目标，提出了以下具体目标。 目标1.利用癌症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AML和MDS基因组研究的前沿。通过对原发性急性髓性白血病（AML）和骨髓增生异常综合征（MDS）基因组测序，我们发现了几个新的涉及DNA甲基化（DNMT 3A和IDH 1）和RNA剪接（U2 AF 1）的基因重复突变。这一基础研究导致了以下两个转化SPORE项目的开发。 项目1。地西他滨反应性的分子决定因素 项目3。骨髓增生异常综合征和AML的RNA剪接调节剂的开发。 目标2.利用当地在免疫学和造血方面的专业知识，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机构的专业知识，导致了两个创新的白血病转化项目的发展。 项目2.急性淋巴细胞白血病骨髓微环境靶向治疗。 项目4。移植物抗宿主病和移植物抗白血病的表观遗传调节。 目标3.加强支持转化性白血病研究的基础设施。此SPORE将支持以下共享研究资源：1）核心A。生物样本处理; 2）核心 B。生物统计学; 3）核心C。局 目标4。招募和培训新的翻译研究人员。 目标5。促进SPORE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.