| |  Online-Ressource |
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| Verfasst von: | Gessner, Anja [VerfasserIn]  |
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| | Thomas, M. [VerfasserIn] |
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| | Garrido Castro, P. [VerfasserIn] |
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| | Büchler, L. [VerfasserIn] |
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| | Scholz, A. [VerfasserIn] |
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| | Brümmendorf, T. H. [VerfasserIn] |
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| | Martínez Soria, Natalia [VerfasserIn] |
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| | Vormoor, J. [VerfasserIn] |
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| | Greil, Johann [VerfasserIn] |
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| | Heidenreich, O. [VerfasserIn] |
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| Titel: | Leukemic fusion genes MLL/AF4 and AML1/MTG8 support leukemic self-renewal by controlling expression of the telomerase subunit TERT |
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| Verf.angabe: | A. Gessner, M. Thomas, P. Garrido Castro, L. Büchler, A. Scholz, T. H. Brümmendorf, N. Martinez Soria, J. Vormoor, J. Greil and O. Heidenreich |
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| E-Jahr: | 2010 |
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| Jahr: | 5 August 2010 |
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| Umfang: | 9 S. |
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| Fussnoten: | Gesehen am 03.03.2023 |
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| Titel Quelle: | Enthalten in: Leukemia |
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| Ort Quelle: | London : Springer Nature, 1997 |
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| Jahr Quelle: | 2010 |
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| Band/Heft Quelle: | 24(2010), 10, Seite 1751-1759 |
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| ISSN Quelle: | 1476-5551 |
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| Abstract: | MLL/AF4 and AML/MTG8 represent two leukemic fusion genes, which are most frequently found in infant acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), respectively. We examined the influence of MLL/AF4 and AML1/MTG8 fusion genes on the expression of TERT coding for the telomerase protein subunit, and subsequently telomerase activity in t(4;11)-positive ALL and t(8;21)-positive cell lines, respectively. MLL/AF4 suppression diminished telomerase activity and expression of TERT. Blocking pro-apoptotic caspase activation in conjunction with MLL/AF4 knockdown enhanced the inhibition of TERT gene expression, which suggests that MLL/AF4 depletion does not reduce TERT expression levels by inducing apoptosis. Knockdown of HOXA7, a direct transcriptional target of MLL/AF4 fusion gene, caused a reduction of telomerase and TERT to an extent similar to that observed with MLL/AF4 suppression. Chromatin immunoprecipitation of SEM cells, using ectopically expressed FLAG-tagged Hoxa7, indicates HOXA7 binding site in the TERT promoter region. Furthermore, suppression of the AML1/MTG8 fusion gene was associated with severely reduced clonogenicity, induction of replicative senescence, impaired TERT expression and accelerated telomere shortening. We thus present findings that show a mechanistic link between leukemic fusion proteins, essential for development and maintenance of leukemia, and telomerase, a key element of both normal and malignant self-renewal. |
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| DOI: | doi:10.1038/leu.2010.155 |
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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/10.1038/leu.2010.155 |
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| | Volltext: https://www.nature.com/articles/leu2010155 |
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| | DOI: https://doi.org/10.1038/leu.2010.155 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Gene regulation |
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| | Leukaemia |
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| | Self-renewal |
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| K10plus-PPN: | 1838101780 |
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| Verknüpfungen: | → Zeitschrift |
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Leukemic fusion genes MLL/AF4 and AML1/MTG8 support leukemic self-renewal by controlling expression of the telomerase subunit TERT / Gessner, Anja [VerfasserIn]; 5 August 2010 (Online-Ressource)
