| |  Online-Ressource |
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| Verfasst von: | Pulikkan, John Anto [VerfasserIn]  |
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| | Müller-Tidow, Carsten [VerfasserIn] |
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| Titel: | CBFβ-SMMHC inhibition triggers apoptosis by disrupting MYC chromatin dynamics in acute myeloid leukemia |
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| Verf.angabe: | John Anto Pulikkan, Mahesh Hegde, Hafiz Mohd Ahmad, Houda Belaghzal, Anuradha Illendula, Jun Yu, Kelsey O’Hagan, Jianhong Ou, Carsten Muller-Tidow, Scot A. Wolfe, Lihua Julie Zhu, Job Dekker, John Hackett Bushweller, Lucio Hernán Castilla |
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| E-Jahr: | 2018 |
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| Jahr: | June 28, 2018 |
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| Umfang: | 37 S. |
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| Fussnoten: | corrected online: July 6, 2018 ; Gesehen am 15.05.2020 |
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| Titel Quelle: | Enthalten in: Cell |
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| Ort Quelle: | [Cambridge, Mass.] : Cell Press, 1974 |
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| Jahr Quelle: | 2018 |
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| Band/Heft Quelle: | 174(2018), 1, Seite 172-186, e1-e21 |
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| ISSN Quelle: | 1097-4172 |
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| Abstract: | The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1. Here, we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. Upon pharmacologic inhibition of the CBFβ-SMMHC/RUNX1 interaction, RUNX1 shows increased binding at three MYC distal enhancers, where it represses MYC expression by mediating the replacement of the SWI/SNF complex component BRG1 with the polycomb-repressive complex component RING1B, leading to apoptosis. Combining the CBFβ-SMMHC inhibitor with the BET inhibitor JQ1 eliminates inv(16) leukemia in human cells and a mouse model. Enhancer-interaction analysis indicated that the three enhancers are physically connected with the MYC promoter, and genome-editing analysis demonstrated that they are functionally implicated in deregulation of MYC expression. This study reveals a mechanism whereby CBFβ-SMMHC drives leukemia maintenance and suggests that inhibitors targeting chromatin activity may prove effective in inv(16) leukemia therapy. |
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| DOI: | doi:10.1016/j.cell.2018.05.048 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.cell.2018.05.048 |
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| | Verlag: http://www.sciencedirect.com/science/article/pii/S0092867418307098 |
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| | DOI: https://doi.org/10.1016/j.cell.2018.05.048 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | acute myeloid leukemia |
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| | CBFb-SMMHC |
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| | CBFbeta |
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| | chromatin |
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| | enhancer |
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| | MYC |
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| | Runx1 |
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| K10plus-PPN: | 1698353448 |
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| Verknüpfungen: | → Zeitschrift |
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CBFβ-SMMHC inhibition triggers apoptosis by disrupting MYC chromatin dynamics in acute myeloid leukemia / Pulikkan, John Anto [VerfasserIn]; June 28, 2018 (Online-Ressource)
