Severe congenital neutropenia terminating in acute myeloid leukemia: disease progression associated with mutations in the granulocyte-colony stimulating factor receptor gene.

Severe congenital neutropenia (SCN) is a heterogeneous disease condition with a variable family history and a propensity to progress towards myelodysplastic syndrome (MDS) and acute myeloblastic leukemia (AML). In a subgroup of patients, point mutations in the G-CSF-R gene have been found. These nonsense mutations result in the truncation of the C-terminal cytoplasmic region, a subdomain that is crucial for G-CSF induced maturation. SCN patients with mutations in the G-CSF-R gene appear to be predisposed to develop AML. Here, we recapitulate our view of how defective G-CSF-R may contribute to neutropenia and leukemogenesis.