TY - JOUR
T1 - The p53 pathway in hematopoiesis
T2 - Lessons from mouse models, implications for humans
AU - Pant, Vinod
AU - Quintás-Cardama, Alfonso
AU - Lozano, Guillermina
PY - 2012/12/20
Y1 - 2012/12/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84871525101&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871525101&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-05-356014
DO - 10.1182/blood-2012-05-356014
M3 - Review article
C2 - 23018641
AN - SCOPUS:84871525101
SN - 0006-4971
VL - 120
SP - 5118
EP - 5127
JO - Blood
JF - Blood
IS - 26
ER -