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Hoxa9 and Meis1 Coo...
Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia.
- Article/chapterEnglish2017
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LIBRIS-ID:oai:gup.ub.gu.se/253422
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https://gup.ub.gu.se/publication/253422URI
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https://doi.org/10.1016/j.ccell.2017.03.001DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression butis currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
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Doebele, Carmen
(author)
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Comoglio, Federico
(author)
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Berg, Tobias
(author)
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Beck, Julia
(author)
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Bohnenberger, Hanibal
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Alexe, Gabriela
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Corso, Jasmin
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Ströbel, Philipp
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Wachter, Astrid
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Beissbarth, Tim
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Schnütgen, Frank
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Cremer, Anjali
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Haetscher, Nadine
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Göllner, Stefanie
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Rouhi, Arefeh
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Palmqvist, Lars,1965Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine(Swepub:gu)xpalla
(author)
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Rieger, Michael A
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Schroeder, Timm
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Bönig, Halvard
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Müller-Tidow, Carsten
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Kuchenbauer, Florian
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Schütz, Ekkehard
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Green, Anthony R
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Urlaub, Henning
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Stegmaier, Kimberly
(author)
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Humphries, R Keith
(author)
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Serve, Hubert
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Oellerich, Thomas
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Göteborgs universitetInstitutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin
(creator_code:org_t)
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In:Cancer cell: Elsevier BV31:41878-36861535-6108
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Mohr, Sebastian
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Doebele, Carmen
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Comoglio, Federi ...
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Berg, Tobias
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Beck, Julia
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Bohnenberger, Ha ...
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Alexe, Gabriela
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Corso, Jasmin
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Ströbel, Philipp
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Wachter, Astrid
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Beissbarth, Tim
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Schnütgen, Frank
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Cremer, Anjali
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Haetscher, Nadin ...
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Göllner, Stefani ...
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Rouhi, Arefeh
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Palmqvist, Lars, ...
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Rieger, Michael ...
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Schroeder, Timm
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Bönig, Halvard
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Müller-Tidow, Ca ...
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Kuchenbauer, Flo ...
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Schütz, Ekkehard
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Green, Anthony R
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Urlaub, Henning
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Stegmaier, Kimbe ...
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Humphries, R Kei ...
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Serve, Hubert
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Oellerich, Thoma ...
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Cancer cell
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University of Gothenburg