The Cytokine Flt3-Ligand in Normal and Malignant Hematopoiesis

Int J Mol Sci. 2017 May 24;18(6):1115. doi: 10.3390/ijms18061115.


The cytokine Fms-like tyrosine kinase 3 ligand (FL) is an important regulator of hematopoiesis. Its receptor, Flt3, is expressed on myeloid, lymphoid and dendritic cell progenitors and is considered an important growth and differentiation factor for several hematopoietic lineages. Activating mutations of Flt3 are frequently found in acute myeloid leukemia (AML) patients and associated with a poor clinical prognosis. In the present review we provide an overview of our current knowledge on the role of FL in the generation of blood cell lineages. We examine recent studies on Flt3 expression by hematopoietic stem cells and its potential instructive action at early stages of hematopoiesis. In addition, we review current findings on the role of mutated FLT3 in leukemia and the development of FLT3 inhibitors for therapeutic use to treat AML. The importance of mouse models in elucidating the role of Flt3-ligand in normal and malignant hematopoiesis is discussed.

Keywords: Flt3; Flt3 with internal tandem duplications (FLT3-ITD); acute myeloid leukemia (AML); cytokines; hematopoiesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Discovery
  • Gene Expression Regulation, Leukemic
  • Hematopoiesis*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / metabolism*
  • Leukemia, Myeloid / pathology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mutation
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism*


  • Membrane Proteins
  • flt3 ligand protein
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3