Interactions of bone marrow microenvironment/niche with leukemia
Hematopoiesis is generated and maintained by hematopoietic stem cells (HSCs) in bone marrow during postnatal life. This process is well controlled by a specialized microenvironment in bone marrow, the so-called HSC niche. The niche consists of various types of cellular niche elements including osteoblasts, adipocytes, endothelial cells, perivascular mesenchymal progenitor cells, mesenchymal stem cells (MSCs), as well as cytokines, growth factors produced by these cells. There is increasing evidence showing that the niche also contributes to the development of myeloid malignancies and drug resistance of leukemia-initiating stem cells (LSCs) which maintain the disease and cause relapse. Thus, targeting bone marrow niche may offer new therapeutic opportunities to improve the efficacy of current therapy for leukemia. However, so far, little is known about how the niche interacts with LSCs and contributes to disease initiation and progression. The primary aim of our research is to understand bone marrow microenvironment/niche contribution to the development of myeloid leukemia including chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) and treatment outcome in patients with the diseases by characterizing leukemia niche in patients and mice. The long-term goal is to identify the niche components that can serve as novel therapeutic targets and prognostic markers for myeloid leukemia. We have been using both patient materials and mouse models. The major technologies used in our projects are multi-colour flow cytometry (FACS), RNA-sequencing, Q-PCR, single cell PCR, confocal imaging, immunohistochemistry, stem cell fate-mapping using mouse models, MSC assays, In vivo and in vitro HSC assays including stem cell transplantation. |