Schematic representation of the disordered bone marrow milieu in sickle cell disease. The inflammatory stimulus represented by fire under the pot is dampened by regular RBC transfusions or allogeneic bone marrow transplantation, which can correct the disordered milieu. HIF-1α, hypoxia inducing factor-1α; RBC, red blood cell; ROS, reactive oxygen species; sVCAM, soluble (circulating) vascular cell adhesion molecule; Tie2, tyrosine kinase with immunoglobulin-like and EGF-like domains 2; VEGF, vascular endothelial growth factor. Professional illustration by Somersault18:24.