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GM-CSF treatment is not effective in congenital neutropenia patients due to its inability to activate NAMPT signaling.
- Source :
-
Annals of hematology [Ann Hematol] 2017 Mar; Vol. 96 (3), pp. 345-353. Date of Electronic Publication: 2016 Dec 14. - Publication Year :
- 2017
-
Abstract
- Severe congenital neutropenia (CN) is a bone marrow failure syndrome characterized by an absolute neutrophil count (ANC) below 500 cells/μL and recurrent, life-threatening bacterial infections. Treatment with granulocyte colony-stimulating factor (G-CSF) increases the ANC in the majority of CN patients. In contrary, granulocyte-monocyte colony-stimulating factor (GM-CSF) fails to increase neutrophil numbers in CN patients in vitro and in vivo, suggesting specific defects in signaling pathways downstream of GM-CSF receptor. Recently, we detected that G-CSF induces granulopoiesis in CN patients by hyperactivation of nicotinamide phosphoribosyl transferase (NAMPT)/Sirtuin 1 signaling in myeloid cells. Here, we demonstrated that, in contrast to G-CSF, GM-CSF failed to induce NAMPT-dependent granulopoiesis in CN patients. We further identified NAMPT signaling as an essential downstream effector of the GM-CSF pathway in myelopoiesis.
- Subjects :
- Cells, Cultured
Congenital Bone Marrow Failure Syndromes
Granulocyte-Macrophage Colony-Stimulating Factor pharmacology
Humans
Myeloid Cells drug effects
Myeloid Cells metabolism
Neutropenia drug therapy
Neutropenia metabolism
Neutrophils drug effects
Neutrophils metabolism
Signal Transduction drug effects
Treatment Outcome
Cytokines metabolism
Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use
Neutropenia congenital
Nicotinamide Phosphoribosyltransferase metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0584
- Volume :
- 96
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Annals of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 27966038
- Full Text :
- https://doi.org/10.1007/s00277-016-2894-5