RAC1 and essential thrombocythemia: Furthermore, we identify several therapeutic compounds inhibiting both early and late signaling mediators such as IGF1R (AG1024), PI3K (AS-703026), MEK (GDC-0941) and Rac1 (NSC23766) that effectively protect against cellular and physiological consequences of ET toxicity in HBMECs and an in vivo mouse challenge model.