PTEN is a tumor suppressor in CML stem cells and BCR-ABL induced leukemias in mice.
Department of Medicine, Division of Hematology/Oncology
Medical Subject Headings
PTEN Phosphohydrolase; Genes, Tumor Suppressor; Stem Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cancer Biology | Life Sciences | Medicine and Health Sciences
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.
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Citation: Blood. 2009 Nov 18. [Epub ahead of print]. Link to article on publisher's website
Leukemia stem cells