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The Paf oncogene is essential for hematopoietic stem cell function and development.

Hematopoietic stem cells (HSCs) self-renew to maintain the lifelong production of all blood populations. Here, we show that the proliferating cell nuclear antigen-associated factor (Paf) is highly expressed in cycling bone marrow HSCs and plays a critical role in hematopoiesis. Mice lacking Paf exhibited reduced bone marrow cellularity; reduced numbers of HSCs and committed progenitors; and leukopenia. These phenotypes are caused by a cell-intrinsic blockage in the development of long-term (LT)-HSCs into multipotent progenitors and preferential loss of lymphoid progenitors caused by markedly increased p53-mediated apoptosis. In addition, LT-HSCs from Paf(-/-) mice had increased levels of reactive oxygen species (ROS), failed to maintain quiescence, and were unable to support LT hematopoiesis. The loss of lymphoid progenitors was likely due the increased levels of ROS in LT-HSCs caused by treatment of Paf(-/-) mice with the anti-oxidant N-acetylcysteine restored lymphoid progenitor numbers to that of Paf(+/+) mice. Collectively, our studies identify Paf as a novel and essential regulator of early hematopoiesis.

Pubmed ID: 21844206


  • Amrani YM
  • Gill J
  • Matevossian A
  • Alonzo ES
  • Yang C
  • Shieh JH
  • Moore MA
  • Park CY
  • Sant'Angelo DB
  • Denzin LK


The Journal of experimental medicine

Publication Data

August 29, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: F31CA130744
  • Agency: NCI NIH HHS, Id: P30-CA 08748

Mesh Terms

  • Acetylcysteine
  • Animals
  • Apoptosis
  • Carrier Proteins
  • Free Radical Scavengers
  • Hematopoiesis
  • Leukopenia
  • Lymphoid Progenitor Cells
  • Mice
  • Mice, Knockout
  • Oncogene Proteins
  • Reactive Oxygen Species
  • Time Factors
  • Tumor Suppressor Protein p53