21) and inv(16) leukemia fusion proteins affect the same RUNX1-miRNA-KIT axis regulating KIT proliferation activity. (A) Scheme based on literature showing the mechanisms that affect RUNX1 function in t(8;21) and inv(16) CBF-AML [1,5,8,9]. (B) A luciferase reporter driven by the miR-221 promoter is activated by RUNX1, alone or in combination with CBFB, while it is repressed by RUNX1-MTG8 or CBFB-MYH11 in transiently transfected U937 cells. (C-D) U937 clones stably expressing either RUNX1-MTG8 (U937RUNX1-MTG8) or CBFB-MYH11 (U937CBFB-MYH11) display a significant increase (p < 0.05) of KIT-positive cells (assessed by CD117 cytofluorimetric analysis in panel C) as well as increased cell proliferation (assessed by EdU incorporation assay in panel D). Shown here one representative clone out of 3 clones stably expressing RUNX1-MTG8 or CBFB-MYH11.