Figure 6.
Figure 6. Critical role of the MYST domain in NUP98-HBO1–driven leukemogenesis in vitro and CMML development in vivo. (A) Schematic of the retrovirus vectors. (B) CFU serial replating assay using CB CD34+ cells transduced with the indicated vectors. Data are presented as mean ± SD from triplicates. (C) Cell proliferation in the liquid culture of the CB CD34+ cells transduced with the indicated vectors. Data are presented as mean ± SD from triplicates. (D) Survival of empty-control (n = 8), HBO1 (n = 6), NUP98-HBO1 (n = 8), and NUP98-HBO1ΔMYST–BMT mice (n = 4). (E) Hoxa9 mRNA and Irf8 mRNA expression in murine BM HSC/Ps transduced with the indicated vectors. Data are presented as mean ± SD from triplicates. (F-G) Acetylation levels of H3 and H4 at the indicated locus of the Hoxa9 (F) and Irf8 gene (G). ChIP-qPCR was performed using BM HSC/Ps transduced with the indicated vectors. In the schematic of HOXA9 promoter region, arrowheads (a to f) indicate the location of the primers. AcH3, acetyl-histone 3; AcH4, acetyl-histone 4; BFU-E, burst forming unit-erythroid; CFU-GM, colony-forming unit granulocyte/monocyte; GEMM, colony-forming unit–granulocyte, erythrocyte, macrophage, megakaryocyte.

Critical role of the MYST domain in NUP98-HBO1–driven leukemogenesis in vitro and CMML development in vivo. (A) Schematic of the retrovirus vectors. (B) CFU serial replating assay using CB CD34+ cells transduced with the indicated vectors. Data are presented as mean ± SD from triplicates. (C) Cell proliferation in the liquid culture of the CB CD34+ cells transduced with the indicated vectors. Data are presented as mean ± SD from triplicates. (D) Survival of empty-control (n = 8), HBO1 (n = 6), NUP98-HBO1 (n = 8), and NUP98-HBO1ΔMYST–BMT mice (n = 4). (E) Hoxa9 mRNA and Irf8 mRNA expression in murine BM HSC/Ps transduced with the indicated vectors. Data are presented as mean ± SD from triplicates. (F-G) Acetylation levels of H3 and H4 at the indicated locus of the Hoxa9 (F) and Irf8 gene (G). ChIP-qPCR was performed using BM HSC/Ps transduced with the indicated vectors. In the schematic of HOXA9 promoter region, arrowheads (a to f) indicate the location of the primers. AcH3, acetyl-histone 3; AcH4, acetyl-histone 4; BFU-E, burst forming unit-erythroid; CFU-GM, colony-forming unit granulocyte/monocyte; GEMM, colony-forming unit–granulocyte, erythrocyte, macrophage, megakaryocyte.

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