The Bone Marrow Microenvironment as Niche Retreats for Hematopoietic and Leukemic Stem Cells

Figure 1

Organization of normal hematopoietic stem cell (HSC) and leukemic stem cell (LSC) niches in the bone marrow. Both HSCs and LSCs establish niches around the bone marrow endosteum and sinusoids. In normal hematopoiesis, the endosteal niche is formed and regulated by osteoblasts, osteoclasts, mesenchymal stromal cells (MSCs), T-regulatory cells (Tregs), and macrophages, while in leukemia, LSCs associate with osteoblasts and mesenchymal stromal cells. HSCs form sinusoidal niches with sinusoidal endothelial cells and leptin receptor-(lepr+-) expressing-perivascular stromal cells. LSCs form sinusoidal niches with sinusoidal endothelial cells. Oxygen gradient decreases from the sinusoids to the endosteum. The normal HSC endosteal niches are hypoxic, while there is an expansion of hypoxic niches in LSC endosteal niches due to LSC proliferation.