title: From cytopenia to leukemia: the role of Gfi1 and Gfi1b in blood formation.
abstract: The DNA-binding zinc finger transcription factors Gfi1 and Gfi1b were discovered more than 20 years ago and are recognized today as major regulators of both early hematopoiesis and hematopoietic stem cells. Both proteins function as transcriptional repressors by recruiting histone-modifying enzymes to promoters and enhancers of target genes. The establishment of Gfi1 and Gfi1b reporter mice made it possible to visualize their cell type-specific expression and to understand their function in hematopoietic lineages. We now know that Gfi1 is primarily important in myeloid and lymphoid differentiation, whereas Gfi1b is crucial for the generation of red blood cells and platelets. Several rare hematologic diseases are associated with acquired or inheritable mutations in the GFI1 and GFI1B genes. Certain patients with severe congenital neutropenia carry mutations in the GFI1 gene that lead to the disruption of the C-terminal zinc finger domains. Other mutations have been found in the GFI1B gene in families with inherited bleeding disorders. In addition, the Gfi1 locus is frequently found to be a proviral integration site in retrovirus-induced lymphomagenesis, and new, emerging data suggest a role of Gfi1 in human leukemia and lymphoma, underlining the role of both factors not only in normal hematopoiesis, but also in a wide spectrum of human blood diseases.
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, Canada; Department de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC, Canada; Division of Experimental Medicine, McGill University, Montréal, QC, Canada; and.
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, Canada; Department of Hematology, Universitätsklinikum Essen, Essen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Vassen
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, Canada;
authors.forename: Brian
authors.initials: B
authors.lastname: Wilkes
authors.affiliation: Institut de recherches cliniques de Montréal, Montréal, QC, Canada; Department of Hematology, Universitätsklinikum Essen, Essen, Germany.
authors.forename: Cyrus
authors.identifier: http://orcid.org/0000-0003-4655-6269
authors.initials: C
authors.lastname: Khandanpour
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000502:physiology; D000080984:Congenital Bone Marrow Failure Syndromes; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D017930:Genes, Reporter; D006402:Hematologic Diseases / Q000235:genetics; D019337:Hematologic Neoplasms / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D042421:Histone Code / Q000502:physiology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D009503:Neutropenia / Q000151:congenital / Q000235:genetics; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016662:Virus Integration
chemical_list: D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; C111977:GFI1B protein, human; C079873:Gfi1 protein, mouse; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors