Blood Journal
Leading the way in experimental and clinical research in hematology

Brief Report
Erk1 and Erk2 are required for maintenance of hematopoietic stem cells and adult hematopoiesis

  1. Gordon Chan1,
  2. Shengqing Gu1,2, and
  3. Benjamin G. Neel1,2
  1. 1Campbell Family Cancer Research Institute, Ontario Cancer Institute and Princess Margaret Hospital, and
  2. 2Department of Medical Biophysics, University Health Network, University of Toronto, Toronto, ON, Canada

Key Points

  • Erk1/2 are required for the maintenance of hematopoietic stem cells and immature progenitors in vivo.

Abstract

Extracellular signal-regulated kinase 1 (Erk1) and Erk2 play crucial roles in cell survival, proliferation, cell adhesion, migration, and differentiation in many tissues. Here, we report that the absence of Erk1 and Erk2 in murine hematopoietic cells leads to bone marrow aplasia, leukopenia, anemia, and early lethality. Mice doubly-deficient in Erk1 and Erk2 show rapid attrition of hematopoietic stem cells and immature progenitors in a cell-autonomous manner. Reconstitution studies show that Erk1 and Erk2 play redundant and kinase-dependent functions in hematopoietic progenitor cells. Moreover, in cells transformed by the oncogenic KRasG12D allele, the presence of either Erk1 or Erk2 with intact kinase activity is sufficient to promote cytokine-independent proliferation.

  • Submitted December 27, 2012.
  • Accepted February 21, 2013.
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