FLT3-ITD mutations are found in 30% of acute myeloid leukemia (AML) and portend a poor prognosis. Patient AML samples with FLT3-ITD express high levels of RUNX1, a transcription factor with known tumor-suppressor function. Using an inducible system, we demonstrate that RUNX1 cooperates with FLT3-ITD to trigger AML and that RUNX1 expression as well as its Tyr-phosphorylation is necessary for both initiation and maintenance of leukemogenesis. Inactivating RUNX1 in tumors released the differentiation block and downregulated genes controlling ribosome biogenesis. We identified Hhex as a direct target of RUNX1 and FLT3-ITD stimulation and confirmed high HHEX expression levels in FLT3-ITD AMLs. Importantly, HHEX could replace RUNX1 in AML induction with FLT3-ITD. These results establish and elucidate the unanticipated oncogenic function of RUNX1 in AML. SOURCE: Kira BehrensRetroviral Pathogenesis Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology

Pluto Bioinformatics

GSE81421: Gene expression signature of Runx1/ lin- sca- kit+ CD105- CD16/32+ CD150+ (XMP) progenitors