Figure 4. Dnmt3a^R878H/+ Npm1^cA/+ MPD progresses to AML following transplantation.

(A) Experimental design for non-competitive secondary transplantation of Dnmt3a^R878H/+ Npm1^cA/+ BM MNCs from primary recipient mice with MDS/MPD or MPD phenotypes. (B) Frequency of donor-derived (CD45.2⁺) cells in PB of secondary recipient mice at 4 wks post-transplant and at time of sacrifice. Dots represent mean ± s.e.m. (MPD, n = 7; MDS/MPD, n = 3). Results are from 3 independent experiments. (C) Overall survival of secondary transplant recipient mice (MPD, n = 7; MDS/MPD, n = 3). (D) WBC, RBC and PLT counts and (E) Spleen weights of moribund mice (control, n = 4; +/+ cA/+, n = 10). (F) Frequency of myeloid, B and T cells within the donor-derived CD45.2⁺ fraction in PB and (G) Gr-1⁺ and Gr-1⁻ cells within donor-derived myeloid PB of moribund mice (control, n = 3; +/+ cA/+, n = 10). (H) Representative Giemsa-stained BM cytospins (far left; 40X, scale bars are 40μm) and H&E-stained spleen (center; 4X, scale bars are 100μm) (inset: 40X, scale bars are 40μm) and liver sections (far right; 4X, scale bars are 100μm) from moribund recipient mice. (I) Somatic, nonsynonymous mutations in individual genes and sets of genes, grouped into five categories. Orange boxes indicate mutations at VAF 0.10–0.39; green boxes, VAF 0.40–0.59; blue boxes, VAF 0.60–0.97. In all graphs unless otherwise specified, dots represent individual mice, bars indicate mean ± s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001.