Figure 7.

Model for OPN-induced dormancy at the endosteum. Cycling ALL blasts migrate to the endosteum in response to niche-specific chemokine expression. Once within the niche, blasts use integrin receptors such as VLA-4 to adhere to extracellular OPN produced locally by osteoblasts. This interaction confines them to the endosteal niche, where blast-derived OPN is also incorporated into the ECM. Additional local niche-specific factors induce cell cycle exit and leukemia dormancy. Dormant blasts that are insensitive to chemotherapy agents that target dividing cells contribute to MRD.