KIT signaling is dispensable for human mast cell progenitor development

Blood. 2017 Oct 19;130(16):1785-1794. doi: 10.1182/blood-2017-03-773374. Epub 2017 Aug 8.

Abstract

Human hematopoietic progenitors are generally assumed to require stem cell factor (SCF) and KIT signaling during differentiation for the formation of mast cells. Imatinib treatment, which inhibits KIT signaling, depletes mast cells in vivo. Furthermore, the absence of SCF or imatinib treatment prevents progenitors from developing into mast cells in vitro. However, these observations do not mean that mast cell progenitors require SCF and KIT signaling throughout differentiation. Here, we demonstrate that circulating mast cell progenitors are present in patients undergoing imatinib treatment. In addition, we show that mast cell progenitors from peripheral blood survive, mature, and proliferate without SCF and KIT signaling in vitro. Contrary to the prevailing consensus, our results show that SCF and KIT signaling are dispensable for early mast cell development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cell Differentiation* / drug effects
  • Cell Proliferation* / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Humans
  • Imatinib Mesylate / pharmacology
  • Mast Cells / drug effects
  • Mast Cells / physiology*
  • Proto-Oncogene Proteins c-kit / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Stem Cells / drug effects
  • Stem Cells / physiology*

Substances

  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit