Fig. 8: Inhibition of RAC2 or PAK1 reverses the tumor-promoting effects of GADD45g deficiency in human MPN cells.

a, b HEL and SET-2 cells were transfected with GADD45g-specific shRNA or shCtrl for 48 h, followed by transfection with RAC2-specific shRNA (shRAC2) or scrambled control (Scr) for another 48 h. Effects of RAC2 knockdown on colony formation (a) and apoptosis (b) of these cells. (c) HEL and SET-2 cells were transfected with GADD45g-specific shRNA or shCtrl for 48 h. Cells were then plated in methylcellulose containing IPA-3 (10 μM). Colonies were counted and analyzed on day 14. d HEL and SET-2 cells were transfected with GADD45g-specific shRNA or shCtrl for 48 h, followed by treatment with vehicle or IPA-3 (10 μM) for 48 h, and the percentage of apoptosis cells was examined. e Effects of EHT 1864 treatment (5 μM for 10–14 days) on colony formation of primary BM CD34⁺ cells from GADD45g^high and GADD45g^low patients with MPN (n = 3 per group). f Effects of IPA-3 treatment (10 μM for 10–14 days) on colony formation of primary BM CD34⁺ cells from GADD45g^high and GADD45g^low patients with MPN (n = 3 per group). For (a–d): Figures shown are representative of three independent experiments with similar results. Data are shown as mean ± SD (n = 3 technical replicates). Comparisons were evaluated by two-tailed Student’s t test, and multiple groups were analyzed with one-way ANOVA.