Downstream Pathway Of Aml1-Eto Targeted Arhgef12 Might Be Targetable For Rock Inhibitor To Improve Therapy Outcome

As a transcription factor AML1-ETO modulate gene expression of its targets. Scanning our ChIP-seq data we found AML1-ETO bind to an AML1 binding motif in the promotor region of ARHGEF12. Exploring acute myeloid leukemia (AML) microarray databases we confirmed that the expression of ARHGEF12 was up-regulated consistently in AML1-ETO-positive AML patient samples. To confirmed this finding, we quantitated expression of ARHGEF12 in pediatric AML samples from Shanghai children's medical center. Not out of expectation, all AML1-ETO-positive cases have higher ARHGEF12. Moreover, the ARHGEF12 expression was an independent poor prognostic factor for overall survival comparing between patients with higher and lower expressed ARHGEF12 (P=0.0258) (Figure A).