NAMPT is essential for the G-CSF-induced myeloid differentiation via a NAD(+)-sirtuin-1-dependent pathway

Nat Med. 2009 Feb;15(2):151-8. doi: 10.1038/nm.1913. Epub 2009 Feb 1.


We identified nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B cell colony enhancing factor (PBEF), as an essential enzyme mediating granulocyte colony-stimulating factor (G-CSF)-triggered granulopoiesis in healthy individuals and in individuals with severe congenital neutropenia. Intracellular NAMPT and NAD(+) amounts in myeloid cells, as well as plasma NAMPT and NAD(+) levels, were increased by G-CSF treatment of both healthy volunteers and individuals with congenital neutropenia. NAMPT administered both extracellularly and intracellularly induced granulocytic differentiation of CD34(+) hematopoietic progenitor cells and of the promyelocytic leukemia cell line HL-60. Treatment of healthy individuals with high doses of vitamin B3 (nicotinamide), a substrate of NAMPT, induced neutrophilic granulocyte differentiation. The molecular events triggered by NAMPT include NAD(+)-dependent sirtuin-1 activation, subsequent induction of CCAAT/enhancer binding protein-alpha and CCAAT/enhancer binding protein-beta, and, ultimately, upregulation of G-CSF synthesis and G-CSF receptor expression. G-CSF, in turn, further increases NAMPT levels. These results reveal a decisive role of the NAD(+) metabolic pathway in G-CSF-triggered myelopoiesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Differentiation / physiology*
  • Cytokines / metabolism*
  • Granulocyte Colony-Stimulating Factor / physiology*
  • Granulocytes / cytology
  • HL-60 Cells
  • Hematopoiesis / drug effects
  • Hematopoiesis / physiology*
  • Humans
  • NAD / physiology*
  • Niacinamide / pharmacology
  • Nicotinamide Phosphoribosyltransferase / metabolism*
  • Receptors, Granulocyte Colony-Stimulating Factor / physiology
  • Sirtuin 1
  • Sirtuins / physiology*


  • Cytokines
  • Receptors, Granulocyte Colony-Stimulating Factor
  • NAD
  • Granulocyte Colony-Stimulating Factor
  • Niacinamide
  • Nicotinamide Phosphoribosyltransferase
  • nicotinamide phosphoribosyltransferase, human
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins