Vorinostat treatment reduces the mutant allele burden in mice. (A) Experimental design for analysis of mutant allele burden after vorinostat treatment. BM from pI:pC-induced MxCre;Jak2V617F/+ mice (CD45.2⁺) was mixed with the BM from WT (CD45.1⁺) mice at a ratio of 3 to 1 (75% V617F vs 25% WT) and injected into lethally irradiated WT CD45.1⁺ recipient animals. Four weeks after transplantation, peripheral blood counts were measured to confirm the establishment of PV disease and chimerism was assessed in the peripheral blood leukocytes by determining the ratio of CD45.2⁺/CD45.1⁺ cells using flow cytometry. Chimeric mice were treated with either placebo or vorinostat (200 mg/kg) for 2 weeks. The ratio of V617F (CD45.2⁺) to WT (CD45.1⁺) progenitors was determined by flow cytometry. (B) Treatment with vorinostat significantly reduced HCT levels in chimeric mice (n = 4). (C) Representative flow cytometry plots of the ratio of V617F (CD45.2⁺) to WT (CD45.1⁺) cells in peripheral blood leukocytes before and after treatment with placebo or vorinostat are shown (left). Bar graphs (right) show that the ratio of V617F to WT cells in Gr-1⁺ cells was dramatically decreased after vorinostat treatment (n = 4). (D) Representative flow cytometry plots of the ratio of V617F (CD45.2⁺) to WT (CD45.1⁺) cells in the BM of chimeric mice after treatment with placebo or vorinostat are shown (left). Bar graphs (right) show that the ratio of V617F to WT cells in Gr-1⁺ cells was significantly decreased in the BM after vorinostat treatment (n = 4). Results shown represent means ± SEM. Asterisks indicate significant differences by Student t test. *P < .05; **P < .005.