Hematopoietic Bone Marrow Microenvironment in Aging and Age-related Leukemia

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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.