Severe neutropenia disorders are characterized by extremely low levels of 
peripheral blood neutrophils, a maturation block of bone marrow progenitor cells 
and recurring severe bacterial and fungal infections. Recent reports indicated 
that severe neutropenia is a consequence of an impaired survival and abnormal 
cell cycle progression of myeloid progenitor cells in both cyclic and severe 
congenital neutropenia. Mutations in the neutrophil elastase gene were 
identified in all patients with cyclic neutropenia and most of the patients with 
severe congenital neutropenia. We hypothesize that expression of mutant 
neutrophil elastase protein results in deregulation of intracellular activity 
and premature cell death of myeloid-committed progenitor cells in these 
disorders, resulting in the lack of peripheral blood neutrophils. The potential 
molecular mechanisms of mutant-protein-mediated neutropenia is discussed.