Jak2^V617F suppresses PP2A activity in a SET-dependent manner. (A) Graph shows PP2A activity in Ba/F3 cells transduced with the MigR1 vector (open bars), Ba/F3 cells expressing low (light gray bars) and high (solid bars) levels of WT and V617F Jak2 kinase, and in HA-PP2A–expressing Ba/F3-Jak2^V617F cells. Inset shows Jak2 levels in Ba/F3 cells transduced with WT or V617F Jak2, and sorted for high and low GFP expression. Western blots (right) show Jak2 expression and activity and PP2Ac expression in vector- and HA-PP2A–transduced Ba/F3-Jak2^V617F cells. (B) PP2A activity in untreated and Jak inhibitor (25 µM AG490; 1 µM Jak inhibitor I; 1 µM TG101348)–treated primary CD34⁺ NBM, PV, PMF, and ET patient samples, Ba/F3-Jak2^V617F and HEL cells. (C) PP2A activity in Jak2 shRNA-expressing HEL cells and SET shRNA-expressing Ba/F3-Jak2^V617F, HEL and primary CD34⁺ PV cells. Inset shows levels of inactive PP2Ac (pY307) in Jak2 shRNA-expressing PV CD34⁺ progenitors. SET downmodulation in SET shRNA-expressing Ba/F3-Jak2^V617F and HEL cells (top right). (D) Percentage of CFC in HEL and Ba/F3-Jak2^V617F cells transduced with empty vector (open bars) or with the SET shRNA (light gray bars), and in HA-PP2Ac–transduced Ba/F3-Jak2^V617F cells (solid bars). *P ≤ .01.