title: Transcription Factor GFI1B in Health and Disease.
abstract: Many human diseases arise through dysregulation of genes that control key cell fate pathways. Transcription factors (TFs) are major cell fate regulators frequently involved in cancer, particularly in leukemia. TheGFI1Bgene, coding a TF, was identified by sequence homology with the oncogene growth factor independence 1 (GFI1). Both GFI1 and GFI1B have six C-terminal C2H2 zinc fingers and an N-terminal SNAG (SNAIL/GFI1) transcriptional repression domain. Gfi1 is essential for neutrophil differentiation in mice. In humans,GFI1mutations are associated with severe congenital neutropenia. Gfi1 is also required for B and T lymphopoiesis. However, knockout mice have demonstrated thatGfi1bis required for development of both erythroid and megakaryocytic lineages. Consistent with this, human mutations ofGFI1Bproduce bleeding disorders with low platelet count and abnormal function. Loss ofGfi1bin adult mice increases the absolute numbers of hematopoietic stem cells (HSCs) that are less quiescent than wild-type HSCs. In keeping with this key role in cell fate,GFI1Bis emerging as a gene involved in cancer, which also includes solid tumors. In fact, abnormal activation ofGFI1BandGFI1has been related to human medulloblastoma and is also likely to be relevant in blood malignancies. Several pieces of evidence supporting this statement will be detailed in this mini review.
authors.affiliation: Hematology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain; Department of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Anguita
authors.affiliation: Microbiology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC) , Madrid , Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Candel
authors.affiliation: Hematology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain; Department of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Chaparro
authors.affiliation: Hematology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain; Department of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Roldán-Etcheverry
keywords: GFI1B; cancer; hematopoiesis; leukemia; platelets disease