Abstract
CCAAT/enhancer binding protein alpha (C/EBPα) induction induces monocytic differentiation even in acute myeloid leukaemia (AML). In this study, the induction/activation of C/EBPα in myelomonocytic AML was investigated using a combination of all-trans retinoic acid (ATRA) and RAD001 (Everolimus), a mammalian target of rapamycin complex 1 (mTORC1) inhibitor. Combining these agents increased PU.1, C/EBPε and C/EBPα expression, increased the p42/p30 C/EBPα ratio, and decreased C/EBPα phosphorylation at serine 21, and was accompanied by growth inhibition, induction of CD11b expression and apoptosis in AML cell lines. Thus, agents that induce sufficient levels of C/EBPα expression might be useful in treating AML.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis / genetics*
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Apoptosis / physiology
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CCAAT-Enhancer-Binding Proteins / genetics
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CCAAT-Enhancer-Binding Proteins / metabolism
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CCAAT-Enhancer-Binding Proteins / physiology*
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Cell Differentiation / drug effects
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Cell Differentiation / genetics*
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Cell Differentiation / physiology
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Cell Line, Tumor
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Child
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Child, Preschool
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Everolimus
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Female
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Gene Expression Regulation, Leukemic / drug effects
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Gene Expression Regulation, Leukemic / physiology
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Humans
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Immunosuppressive Agents / pharmacology
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Leukemia, Myelomonocytic, Acute / genetics*
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Leukemia, Myelomonocytic, Acute / metabolism
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Leukemia, Myelomonocytic, Acute / pathology
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Monocytes / drug effects
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Monocytes / metabolism
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Monocytes / physiology*
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Phosphorylation / drug effects
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RNA Processing, Post-Transcriptional / drug effects
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RNA Processing, Post-Transcriptional / physiology
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Sirolimus / analogs & derivatives
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Sirolimus / pharmacology
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Tretinoin / pharmacology
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U937 Cells
Substances
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CCAAT-Enhancer-Binding Proteins
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CEBPA protein, human
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Immunosuppressive Agents
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Tretinoin
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Everolimus
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Sirolimus