Abstract
Chronic myeloid leukemia (CML) is initiated from the BCR-ABL-expressing leukemia stem cells (LSCs). These LSCs are highly resistant to BCR-ABL kinase inhibitors, imatinib, dasantinib and nilotinib, and methods for eradication of LSCs are still not available. It is critical to identify genes that play roles in survival and proliferation of LSCs. We recently discovered that the tumor suppressor gene Pten is downregulated in LSCs of CML mice. By genetic deletion or overexpression of Pten, we confirmed that Pten functions as a tumor suppressor in LSCs of CML, consistent with the role of Pten in LSCs of acute myeloid leukemia (AML) and progenitor cells of T-ALL progenitors. Functional enhancement of the Pten pathway provides a therapeutic strategy for targeting LSCs.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzamides
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Dasatinib
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Drug Resistance, Neoplasm
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Genes, Tumor Suppressor
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Humans
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Imatinib Mesylate
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
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Leukemia, Myeloid, Acute / drug therapy
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Leukemia, Myeloid, Acute / enzymology*
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Leukemia, Myeloid, Acute / pathology
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Mice
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Neoplastic Stem Cells / enzymology*
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Neoplastic Stem Cells / pathology
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism*
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Piperazines / therapeutic use
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Pyrimidines / therapeutic use
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Signal Transduction
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Thiazoles / therapeutic use
Substances
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Benzamides
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Piperazines
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Pyrimidines
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Thiazoles
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Imatinib Mesylate
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PTEN Phosphohydrolase
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nilotinib
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Dasatinib