PATHOPHYSIOLOGY OF KOSTMANN-SYNDROME - THE G-CSF RECEPTOR ISSUE

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