Pathophysiology of Kostmann syndrome: the G-CSF receptor issue

Kostmann Syndrome is defined as a chronic neutropenia, dating from early childhood, characterized typically by a granulopoeisis impairment at the promyelocyte stage. The origin is not yet understood. G-CSF receptor anomaly -the intra-cellular carboxy terminal region- was noted in a few patients (6 out of 54), initially in two patients who later developed secondary leukemia. More follow-up, with other patients, led us to consider the mutation of the G-CSF receptor sometimes as a transient event, not systematically resulting in malignancy. This finding directs research toward intra-cellular signaling pathway in a pathology that raises questions both of granulopoeisis and leukemogenesis.