Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome

Haematologica. 2018 Apr;103(4):614-625. doi: 10.3324/haematol.2017.167288. Epub 2018 Jan 11.


Differentiation of hematopoietic stem cells is regulated by a concert of different transcription factors. Disturbed transcription factor function can be the basis of (pre)malignancies such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Growth factor independence 1b (Gfi1b) is a repressing transcription factor regulating quiescence of hematopoietic stem cells and differentiation of erythrocytes and platelets. Here, we show that low expression of Gfi1b in blast cells is associated with an inferior prognosis of MDS and AML patients. Using different models of human MDS or AML, we demonstrate that AML development was accelerated with heterozygous loss of Gfi1b, and latency was further decreased when Gfi1b was conditionally deleted. Loss of Gfi1b significantly increased the number of leukemic stem cells with upregulation of genes involved in leukemia development. On a molecular level, we found that loss of Gfi1b led to epigenetic changes, increased levels of reactive oxygen species, as well as alteration in the p38/Akt/FoXO pathways. These results demonstrate that Gfi1b functions as an oncosuppressor in MDS and AML development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epigenomics
  • Forkhead Box Protein O1 / metabolism
  • Gene Deletion
  • Heterozygote
  • Homozygote
  • Humans
  • Leukemia, Myeloid, Acute / etiology*
  • Mice
  • Myelodysplastic Syndromes / etiology*
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Repressor Proteins / deficiency
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Forkhead Box Protein O1
  • Foxo1 protein, mouse
  • GFI1B protein, human
  • Proto-Oncogene Proteins
  • Reactive Oxygen Species
  • Repressor Proteins
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases