4.2 Article

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

Journal

CURRENT OPINION IN HEMATOLOGY
Volume 17, Issue 4, Pages 300-307

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOH.0b013e32833a06f8

Keywords

growth factor independent-1; hematopoiesis; HoxA9; leukemia; Pu.1; severe congenital neutropenia; transcription

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Funding

  1. NIH [CA142601, HL079574]
  2. Leukemia and Lymphoma Society of America
  3. Alex's Lemonade Stand

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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.

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