Setd2 deficiency accelerates leukemia progression in secondary transplantation and JIB-04 regulates proliferation and apoptosis of SKM-1 cells. (A) Survival curves of the mice that underwent secondary BM transplantation from the NHD13 (n = 16; median survival, 77 days) or NHD13/Setd2Δ/Δ (n = 13; median survival, 16 days) leukemic mice. (B) Complete blood count (CBC) analysis of NHD13 and NHD13/Setd2Δ/Δ leukemic BM in the WT and secondary transplant-recipient mice. CBCs were obtained 16 days after transplantation. RBC, red blood cell. (C) Wright’s staining of PB, BM, and spleen cells isolated from mice receiving the NHD13 and NHD13/Setd2Δ/Δ leukemic BM for 16 days. (D) Images of the spleens and livers isolated from the mice receiving NHD13 or NHD13/Setd2Δ/Δ leukemic BM for 16 days. (E) Representative flow cytometry profiles of Gr-1 and c-Kit expression of the BM and spleen cells of the mice receiving NHD13 or NHD13/Setd2Δ/Δ leukemic BM for 16 days. (F) Hematoxylin and eosin staining of the BM, spleen, and liver of the mice receiving NHD13 or NHD13/Setd2Δ/Δ leukemic BM for 16 days. (G) Western blot analysis of H3K36me3 in the JIB-04 (1 μM) or dimethyl sulfoxide–treated SKM-1 cells. (H) MTT analysis of the JIB-04 (1 μM) or dimethyl sulfoxide–treated SKM-1 cells. (I-J) Representative flow cytometry analysis (I) and quantification of the frequencies (J) of the apoptotic SKM-1 cells. *P < .05; **P < .01; ***P < .001; ****P < .0001.