Gfi1-cells and circuits: unraveling transcriptional networks of development and disease

Curr Opin Hematol. 2010 Jul;17(4):300-7. doi: 10.1097/MOH.0b013e32833a06f8.

Abstract

Purpose of review: The review will integrate current knowledge of transcriptional circuits whose dysregulation leads to autoimmunity, neutropenia and leukemia.

Recent findings: Growth factor independent-1 (Gfi1) is a transcriptional repressor with essential roles in controlling hematopoietic stem cell biology, myeloid and lymphoid differentiation and lymphocyte effector functions. Recent work has suggested that Gfi1 competes or collaborates with other transcription factors to modulate transcription programs and lineage decisions.

Summary: Gfi1 is central to several transcriptional circuits whose dysregulation leads to abnormal or malignant hematopoiesis. These functional relationships are conserved from Drosophila development. Such conserved pathways represent central oncogenic or 'gatekeeper' pathways that are pivotal to understanding the process of cellular transformation, and illustrate key targets for clinical intervention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Regulatory Networks
  • Hematopoiesis / genetics
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Leukemia / genetics
  • Leukemia / physiopathology
  • Neutropenia / genetics
  • Neutropenia / physiopathology
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • DNA-Binding Proteins
  • GFI1 protein, human
  • Transcription Factors