PTEN is a tumor suppressor in CML stem cells and BCR-ABL induced leukemias in mice.
Student Authors
Haojian ZhangUMass Chan Affiliations
Department of Medicine, Division of Hematology/OncologyDocument Type
Journal ArticlePublication Date
2009-11-18Keywords
PTEN Phosphohydrolase; Genes, Tumor Suppressor; Stem Cells; Leukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia stem cells
Cancer Biology
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The tumor suppressor gene PTEN is inactivated in many human cancers. However, it is unknown whether PTEN functions as a tumor suppressor in human Philadelphia chromosome positive (Ph(+)) leukemia that includes chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL) and is induced by the BCR-ABL oncogene. Using our mouse model of BCR-ABL induced leukemias, we show that PTEN is down-regulated by BCR-ABL in leukemia stem cells (LSCs) in CML, and that PTEN deletion causes acceleration of CML development. In addition, overexpression of PTEN delays the development of CML and B-ALL, and prolongs survival of leukemia mice. PTEN suppresses LSCs and induces cell cycle arrest of leukemia cells. Moreover, PTEN suppresses B-ALL development through regulating its downstream gene Akt1. These results demonstrate a critical role of PTEN in BCR-ABL induced leukemias and suggest a potential strategy for the treatment of Ph(+) leukemia.Source
Blood. 2009 Nov 18. [Epub ahead of print]. Link to article on publisher's websiteDOI
10.1182/blood-2009-06-228130Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33088PubMed ID
19965668Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1182/blood-2009-06-228130