GM-CSF is not able to induce granulopoiesis in CN patients due to absence of LEF-1 transcription factor

G-CSF is successfully used to treat patients with severe congenital neutropenia (CN). However, daily treatment with high doses of G-CSF (up to 50µg/kg/d) are required to induce granulocyte numbers of above 1000/µl in CN patients. Intriguingly, GM-CSF failed even at high dosages (30µg/kg/day) to increase the neutrophil numbers, but led to a dramatic increase of eosinophils and monocytes in those patients. We aimed to investigate the mechanisms of abrogated GM-CSF-triggered granulopoiesis in CN patients. Recently, we found that in CN patients “steady-state” granulopoiesis could not be activated due to a lack of LE…