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Blood. 2010 Jan 21;115(3):626-35. doi: 10.1182/blood-2009-06-228130. Epub 2009 Nov 18.

PTEN is a tumor suppressor in CML stem cells and BCR-ABL-induced leukemias in mice.

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  • 1Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.

Abstract

The tumor suppressor gene phosphatase and tensin homolog (PTEN) is inactivated in many human cancers. However, it is unknown whether PTEN functions as a tumor suppressor in human Philadelphia chromosome-positive leukemia that includes chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL) and is induced by the BCR-ABL oncogene. By using our mouse model of BCR-ABL-induced leukemias, we show that Pten is down-regulated by BCR-ABL in leukemia stem cells 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 leukemia stem cells 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 Philadelphia chromosome-positive leukemia.

PMID:
19965668
PMCID:
PMC2810991
DOI:
10.1182/blood-2009-06-228130
[PubMed - indexed for MEDLINE]
Free PMC Article
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