PTEN is a tumor suppressor in CML stem cells and BCR-ABL induced leukemias in mice.
Student AuthorsHaojian Zhang
UMass Chan AffiliationsDepartment of Medicine, Division of Hematology/Oncology
Document TypeJournal Article
KeywordsPTEN Phosphohydrolase; Genes, Tumor Suppressor; Stem Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia stem cells
Medicine and Health Sciences
MetadataShow full item record
AbstractThe 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.
SourceBlood. 2009 Nov 18. [Epub ahead of print]. Link to article on publisher's website
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/33088
Related ResourcesLink to article in PubMed