Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia

@inproceedings{Mohr2017Hoxa9AM,
  title={Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia},
  author={Sebastian Mohr and Carmen Doebele and Federico Comoglio and Tobias Berg and Julia Beck and Hanibal Bohnenberger and Gabriela Alexe and Jasmin Corso and Philipp Stroebel and Astrid Wachter and Tim Bei{\ss}barth and Frank Schn{\"u}tgen and Anjali Cremer and Nadine Haetscher and Stefanie G{\"o}llner and Arefeh Rouhi and Lars Palmqvist and Michael A. Rieger and Timm Schroeder and Halvard Boenig and Carsten M{\"u}ller-Tidow and Florian Kuchenbauer and Ekkehard Sch{\"u}tz and Anthony R Green and Henning Urlaub and Kimberly Stegmaier and Richard Keith Humphries and Hubert Serve and Thomas Oellerich},
  booktitle={Cancer cell},
  year={2017}
}
The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is 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… CONTINUE READING

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