Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppression of Mir-146a in Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is driven by cell populations with stem cell-like characteristics, so called leukemia stem cells (LSC). The transcription factor Meis1 is one of the critical regulators of LSC and is capable to rapidly induce AML in murine models in the context of Hox gene overexpression. Despite sophisticated studies identifying Hox- and Meis1-regulated genes, the knowledge about their impact on intracellular signaling pathways and its functional consequences is still limited. Since Hox and Meis1 gene overexpression is often found in high risk AML and since both factors are currently considered as undruggable, we aimed to elucidate their role in regulating intracellular signaling and to investigate, if cells transformed by Hoxa9 and Meis1 are addicted to certain signaling processes.