The role of NAMPT/SIRT1/FOXO3a pathway for the leukemic transformation in severe congenital neutropenia (CN) patients.

Severe congenital neutropenia is a heterogeneous disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5×10/l. G-CSF treatment increases blood neutrophil numbers in more than 90% of individuals with congenital neutropenia. CN is also considered as a pre-leukemic syndrome, since ca. 20% of CN patients develop AML/MDS. Recently we found that NAMPT, a protein involved in biosynthesis of NAD+ was significantly increased in CN patients treated with G-CSF as compared to healthy individuals (Skokowa et al,…