PTEN in the haematopoietic system and its therapeutic indications.
A unique feature of the haematopoietic system is its self-renewal ability while maintaining a stable number of pluripotent haematopoietic stem cells (HSCs). Recently, two publications by Yilmaz and colleagues and Zhang and colleagues demonstrated that the loss of the tumour suppressor phosphatase and tensin homolog (PTEN) in mice disturbed the maintenance of quiescent HSCs and promoted leukemogenesis. Mammalian target of rapamycin (mTOR) inhibition with rapamycin distinctly rescued HSC development and depleted leukemic stem cells. Thus, the regulation of HSCs and leukemic cells seems to be governed by cell-context-dependent, PTEN-mediated regulation of mTOR.
Cheung
Alison M
AM
The Campbell Family Institute for Breast Cancer Research, 620 University Avenue, Suite 706, Toronto, Ontario M5G 2C1, Canada.
Mak
Tak W
TW
D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases
D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D020123:Sirolimus