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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.
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Mohr, Sebastian (author)
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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 (author)
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Alexe, Gabriela (author)
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Corso, Jasmin (author)
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Ströbel, Philipp (author)
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Wachter, Astrid (author)
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Beissbarth, Tim (author)
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Schnütgen, Frank (author)
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Cremer, Anjali (author)
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Haetscher, Nadine (author)
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Göllner, Stefanie (author)
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Rouhi, Arefeh (author)
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- Palmqvist, Lars, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
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Rieger, Michael A (author)
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Schroeder, Timm (author)
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Bönig, Halvard (author)
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Müller-Tidow, Carsten (author)
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Kuchenbauer, Florian (author)
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Schütz, Ekkehard (author)
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Green, Anthony R (author)
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Urlaub, Henning (author)
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Stegmaier, Kimberly (author)
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Humphries, R Keith (author)
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Serve, Hubert (author)
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Oellerich, Thomas (author)
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English.
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In: Cancer cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 31:4
- Related links:
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http://www.cell.com/...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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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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show more...
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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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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Cancer cell
- By the university
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University of Gothenburg