Hematopoietic Bone Marrow Microenvironment in Aging and Age-related Leukemia

衰老和年龄相关性白血病中的造血骨髓微环境

• 批准号: 9356958
• 负责人: OLIN D. Liang
• 金额: $ 22.87万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9356958
• 关键词: ATAC-seq; Acute Myelocytic Leukemia; Affect; Aging; Alpha Cell; Blood; Blood Cells; Bone Marrow; Bone Marrow Cells; Bone Marrow Transplantation; Cell Aging; Cell Differentiation process; Cells; Characteristics; Chromatin; Complex; Cues; Development; Disease; Dysmyelopoietic Syndromes; Elderly; Elements; Endothelial Cells; Enzymes; Epigenetic Process; Future; Genetic; Goals; Hematological Disease; Hematopoiesis; Hematopoietic; Hematopoietic System; Hematopoietic stem cells; Immune response; Impairment; Incidence; Intercept; Knock-out; Knockout Mice; Lipids; Malignant - descriptor; Malignant Neoplasms; Mesenchymal; Modeling; Mus; Myelodysplastic/Myeloproliferative Disease; Myelofibrosis; Myelogenous; Myeloproliferative disease; Nature; PDGFRB gene; Pathologic; Patients; Pericytes; Phenotype; Phosphoric Monoester Hydrolases; Population; Public Health; Reporter; Role; Site; Stem cells; Stromal Cells; Techniques; Transplant Recipients; Transplantation; Treatment outcome; Work; age related; aged; bone aging; cell type; clinically relevant; effective therapy; experimental study; improved; in vivo; inositol-1,4,5-trisphosphate 5-phosphatase; leukemia; novel strategies; osteochondral tissue; reconstitution; small molecule inhibitor; treatment strategy; trend

Project Summary/Abstract: The increasing number of elderly people affected by age-related blood malignancies, mainly of the myeloid subtype, is one of the most significant public health challenges today but currently there are no effective treatments. The overall objective of this project is to investigate the role of bone marrow microenvironment in hematopoiesis and age-related leukemia. We previously discovered that deficiency of the lipid phosphatase SHIP enables long-term reconstitution of the hematopoietic bone marrow microenvironment. This proposed study is a continuation of our prior work. We will investigate the role of aged bone marrow microenvironment in normal hematopoiesis (Aim 1), identify and functionally evaluate critical cell types for the hematopoietic niche (Aim 2), and reconstitute aged and pre-leukemic bone marrow microenvironment via SHIP inhibition in vivo (Aim 3). The long-term goal of this project is to develop novel strategies for treatment of deadly blood diseases such as myelodysplastic syndromes, myeloproliferative neoplasms, myelofibrosis and acute myeloid leukemia in elderly people.

项目摘要/摘要： 受年龄相关的血液恶性肿瘤影响的老年人越来越多，主要是 髓样亚型，是当今最重大的公共卫生挑战之一，但目前没有 有效的治疗方法。该项目的总体目的是研究骨髓的作用 造血和与年龄有关的白血病的微环境。我们以前发现 脂质磷酸酶船可以长期重构造血骨髓微环境。 这项拟议的研究是我们先前工作的延续。我们将研究老化的骨髓的作用 正常造血的微环境（AIM 1），识别并在功能上评估关键细胞类型 造血生态位（AIM 2），并通过船重新建立了老化和白血病前的骨髓微环境 抑制体内（目标3）。该项目的长期目标是制定新的策略来治疗 致命的血液疾病，例如骨髓增生综合征，骨髓增生性肿瘤，骨髓纤维化和 老年人的急性髓样白血病。