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

The p53 pathway in hematopoiesis: lessons from mouse models, implications for humans

  1. Vinod Pant1,
  2. Alfonso Quintás-Cardama2, and
  3. Guillermina Lozano1
  1. Departments of 1Genetics and
  2. 2Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX

Abstract

Aberrations in the p53 tumor suppressor pathway are associated with hematologic malignancies. p53-dependent cell cycle control, senescence, and apoptosis functions are actively involved in maintaining hematopoietic homeostasis under normal and stress conditions. Whereas loss of p53 function promotes leukemia and lymphoma development in humans and mice, increased p53 activity inhibits hematopoietic stem cell function and results in myelodysplasia. Thus, exquisite regulation of p53 activity is critical for homeostasis. Most of our understanding of p53 function in hematopoiesis is derived from genetically engineered mice. Here we summarize some of these models, the various mechanisms that disrupt the regulation of p53 activity, and their relevance to human disease.

  • Submitted May 25, 2012.
  • Accepted September 20, 2012.
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