Hematopoietic Bone Marrow Microenvironment in Aging and Age-related Leukemia

项目摘要/摘要： 越来越多的老年人受到年龄相关性血液恶性肿瘤的影响，主要是 髓系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。这个项目的总体目标是研究骨髓的作用 造血微环境与年龄相关性白血病。我们之前发现，人的心理缺陷 脂质磷酸酶SHIP能够长期重建造血骨髓微环境。 这项拟议的研究是我们先前工作的延续。我们将研究衰老骨髓的作用 正常造血中的微环境(目标1)，识别和功能评估关键细胞类型 造血生态位(目标2)，并通过SHIP重建老年和白血病前期骨髓微环境 体内抑制(目标3)。该项目的长期目标是开发新的治疗方法。 致命的血液疾病，如骨髓增生异常综合征、骨髓增生性肿瘤、骨髓纤维化和 老年人的急性髓系白血病。

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.