The interaction of acute myeloid leukemia (AML) blasts with the bone marrow microenvironment regulates critical processes important in sustaining the malignant clone including self-renewal, cell growth, and proliferation as well as resistance to chemotherapy. The chemokine receptor, CXC receptor 4 (CXCR4), with its ligand chemokine ligand 12 (CXCL12), is the principal regulator of trafficking of normal and malignant stem cells to the bone marrow. High expression of CXCR4 on AML blasts has been identified as an adverse prognostic feature in AML. s a target for therapeutic intervention, preclinical studies have demonstrated in animal models the potential for CXCR4 antagonists to potentiate the effect of chemotherapy in AML and tyrosine kinase inhibitors in AML. Based on these studies, clinical trials have been initiated in AML with CXCR4 inhibitors in combination with either chemotherapy or FMS-like tyrosine kinase 3 (FLT3) inhibitors.
- Bone marrow microenvironment · Stem cell mobilization
- Chemokine receptor
- G-protein-coupled receptor