Dnmt3a^−/−;Idh2^R140QHSPCs overproduced PGE2 and were sensitive to prostaglandin synthesis and signaling inhibition. (A) Metabolomics profiling of 4 genotypes in 5 million donor-derived c-kit⁺ bone marrow cells. Relative abundance of metabolites is shown in the heat map. (B) Relative arachidonic acid level in c-kit⁺ bone marrow cells from 3aKO-140, 3aKO and WT relative to WT-140 from panel A. Mean ± standard deviation (SD; n = 3 per group); ***P < .001, compared with WT-140, by Student t test. (C) Amount of prostaglandin E2 secreted into the culture medium by c-kit⁺ cells from the 4 genotypes. *P < .05; ***P < .01, compared with WT, by 1-way ANOVA and post hoc Bonferroni test. (D) Active chromatin state of 3aKO-140 and WT MEP at the Ptgs2 and Ptger3 loci. (E) Experimental scheme of prostaglandin compound test. (F-H) Growth inhibition (F) and differentiation induction (G-H) in 3aKO-140 cells treated with 10 μM celecoxib and 10 μM L-798 106. Mean ± SD is shown (n = 3 per group). **P < .01, by Student t test. Three biological replicates were performed for each group. Representative flow plot is shown. (I) The growth curve of Dnmt3aKO c-kit⁺ bone marrow cells under DMSO and 10 μM celecoxib treatment. Mean ± SD (n = 3 per group). (J) The growth curve of WT-IDH2^R140Q c-kit⁺ bone marrow cells under DMSO and 10 μM celecoxib treatment. Mean ± SD (n = 3 per group).