Brd4 inhibition abrogates the MF-initiating capacity of JAK2^V617F/Ezh2^Δ/Δ cells. (a) Experimental scheme of the JQ1 treatment of chimeric mice reconstituted with WT and mutant cells. (b) Fold changes in chimerism of CD45.2⁺ mutant cells in Mac1⁺ myeloid cells in the PB of recipients (n = 5 each) 8 wk after JQ1 administration compared with that of pre-JQ1 administration (red bars show the mean). (c) Experimental scheme of the JQ1 treatment of WT mice and JAK2^V617F/Ezh2^Δ/Δ mice. (d) Hemoglobin levels of WT (open circles) and JAK2^V617F/Ezh2^Δ/Δ (closed circles) mice pretreatment and 7 d after the completion of the JQ1 treatment. (e) Histology and fibrosis grading (grade 0–3) of the BM from DMSO-treated (n = 7) and JQ1-treated (n = 6) JAK2^V617F/Ezh2^Δ/Δ mice observed by silver staining. Bars, 50 µm. (f) Spleen weight of DMSO-treated (n = 5) or JQ1-treated (n = 4) JAK2^V617F/Ezh2^Δ/Δ mice 4 wk after the end of the treatment. (g) Proportions of LSKs and MkPs in the spleen of DMSO-treated and JQ1-treated JAK2^V617F/Ezh2^Δ/Δ mice 4 wk after the completion of the treatment. (h and i) Chimerism of CD45.2⁺ cells in the PB (h) and BM LSKs, spleen LSKs, and spleen MkPs (i) of CD45.1⁺ recipients (n = 5 each) at 4 mo after transplantation of 10⁶ spleen cells isolated from DMSO-treated or JQ1-treated WT and JAK2^V617F/Ezh2^Δ/Δ mice. (d and f–i) Bars and asterisks show the mean ± SEM and *, P < 0.05 by the Student’s t test (d and f–h) or *, P < 0.05 and **, P < 0.01 by the Mann–Whitney U test (i); two independent experiments.