Abstract
Activating mutations in NOTCH1 consitute the most prominent genetic abnormality in T-cell acute lymphoblastic leukemia (T-ALL). However, most T-ALL cell lines with NOTCH1 mutations are resistant to treatment with γ-secretase inhibitors (GSIs). The spotlight is now shifting to the phosphatidylinositide 3-kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome ten (PTEN)/AKT/mammalian target of rapamycin (mTOR) pathway as another key potential target. These two signaling routes are deregulated in many types of cancer. In this review we discuss these two pathways with respect to their signaling mechanisms, functions during T-cell development, and their mutual roles in the development of T-ALL.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Gene Expression Regulation, Leukemic
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Humans
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Molecular Targeted Therapy
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism*
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism*
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / enzymology
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / therapy
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism*
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Receptors, Notch / genetics
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Receptors, Notch / metabolism*
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Signal Transduction
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T-Lymphocytes / cytology
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T-Lymphocytes / metabolism*
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism*
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Thymus Gland / metabolism
Substances
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Receptors, Notch
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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PTEN Phosphohydrolase
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PTEN protein, human