Abstract
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. To identify novel candidates for targeted therapy, we performed a comprehensive transcriptome analysis identifying MondoA (MLXIP) - a transcription factor regulating glycolysis - to be overexpressed in ALL compared to normal tissues. Using microarray-profiling, gene-set enrichment analysis, RNA interference and functional assays we show that MondoA overexpression increases glucose catabolism and maintains a more immature phenotype, which is associated with enhanced survival and clonogenicity of leukemia cells. These data point to an important contribution of MondoA to leukemia aggressiveness and make MondoA a potential candidate for targeted treatment of ALL.
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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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / physiology*
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Cell Differentiation / drug effects
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Cell Differentiation / genetics*
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Cell Survival / drug effects
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Cell Survival / genetics
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Drug Evaluation, Preclinical
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Gene Expression Profiling
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Gene Expression Regulation, Leukemic / drug effects
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Hep G2 Cells
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Humans
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Jurkat Cells
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Microarray Analysis
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Neoplasm Invasiveness
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / physiopathology
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RNA, Small Interfering / pharmacology
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Tumor Cells, Cultured
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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MLXIP protein, human
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RNA, Small Interfering