Abstract
Notch activation is a current event in T Acute Lymphoblastic Leukemia (T-ALL) but the downstream elements that are able to support Notch-dependent leukemias are not well characterized. We have recently shown that the Notch-Hes1-CYLD-NFkB axis is crucial in the maintenance of T-ALL, but detailed evaluation of the contribution of each one of these elements is still missing. Here we use a Notch1-induced leukemia in vivo model to study the effect of silencing the Notch-target gene, Hes1, or over-expressing the Hes1-target, CYLD. We here show that both strategies completely abolish the ability of constitutive active Notch1 to generate T-ALL.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Cell Line
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Cell Transformation, Neoplastic / genetics*
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Cysteine Endopeptidases / metabolism*
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DNA Primers / genetics
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Deubiquitinating Enzyme CYLD
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Flow Cytometry
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Gene Expression Regulation / physiology
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Homeodomain Proteins / metabolism*
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Humans
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Leukemia, T-Cell / etiology
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Leukemia, T-Cell / metabolism*
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Mice
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Mice, Inbred C57BL
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Receptor, Notch1 / genetics
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Receptor, Notch1 / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factor HES-1
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Transduction, Genetic
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA Primers
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Hes1 protein, mouse
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Homeodomain Proteins
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Receptor, Notch1
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Transcription Factor HES-1
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CYLD protein, mouse
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Deubiquitinating Enzyme CYLD
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Cysteine Endopeptidases