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

• Published in: Blood Vol. 120; no. 26; pp. 5118 - 5127
• Main Authors: Pant, Vinod, Quintás-Cardama, Alfonso, Lozano, Guillermina
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 20.12.2012; Americain Society of Hematology; American Society of Hematology
• Subjects: Animals; Biological and medical sciences; Hematologic and hematopoietic diseases; Hematologic Diseases - blood; Hematologic Diseases - genetics; Hematologic Diseases - pathology; Hematopoiesis - genetics; Hematopoiesis - physiology; Humans; Learning; Medical sciences; Mice; Models, Animal; Models, Biological; Review; Signal Transduction - genetics; Signal Transduction - physiology; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Protein p53 - physiology; Human; Animal model; Vertebrata; Mammalia; TP53 Gene; Hematology; Mouse; Hematopoiesis; Rodentia; Tumor suppressor gene
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2012-05-356014

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.