Inherited disorders of granulopoiesis: understanding pathogenesis to advance new therapies

The central importance of neutrophils for human health is clearly demonstrated by the clinical presentation of patients with severe congenital neutropenia (CN) and cyclic neutropenia (CyN). The majority of patients with CN with neutropenia as their only symptom do not survive the first year of life unless they are treated with recombinant human cytokine granulocyte colony-stimulating factor (rhG-CSF) or undergo allogeneic bone marrow transplantation. Understanding the processes of defective granulopoiesis downstream of CN-associated gene mutations sheds light on the mechanisms that regulate granulopoiesis and granulocyte functions. Furthermore, given that CN is a preleukemia syndrome, studying CN can help to define the role of defective granulopoiesis and deregulated neutrophil functions in leukemogenesis. The development of advanced experimental models of CN and CyN overcomes the limitations of insufficient patient material for research, leading to breakthroughs in the understanding of their pathogenesis and the development of new potential therapies.