Deletion of Jak2 is more effective than JAK inhibitor therapy at reducing disease burden.MPLW515L-transduced mice were treated with vehicle, 60 mg/kg ruxolitinib or pI:pC to excise Jak2. (A) Deletion of Jak2 led to significant reduction in mutant allele burden in BM as compared with inhibitor treatment (P < .005). It also resulted in further decrease in (B) blood counts and (C) spleen size in Jak2-deleted mice compared with mice that received ruxolitinib alone (P < .005). (D) Loss of JAK2 also leads to reduction in MEP and CD11b⁺Gr⁺ proportions with a dramatic decrease in the contribution of mutant (GFP⁺) cells. (Data are represented at mean ± SEM; vehicle, n = 5; Rux, n = 9; Jak2 deleted, n = 6).