Figure 3: Ezh2 loss promotes initiation and propagation of RUNX1S291fs-induced MDS.

(a) Representative flow cytometric profiles of LSK cells in recipient mice infused with 2 × 10⁴ Rx291 or Rx291/Ezh2^Δ/ΔLin⁻c-Kit⁺ cells at 6 months post transplantation. Proportion of CD45.2⁺GFP⁺ cells within LSK cells was indicated (%). (b) Dysplastic neutrophils, red blood cells and megakaryocytes in the BM of the positively repopulated recipient mice in a that developed MDS. Scale bar, 10 μm. (c) Significantly shorter median survival of recipients of Rx291/Ezh2^Δ/Δ-MDS cells (n=8), compared with those of Rx291-MDS cells (n=8)(72.5 days versus 165 days; P<0.0001 by Log-rank test). Lethally irradiated recipient mice were infused with 1 × 10⁶ CD45.2⁺GFP⁺ RUNX1S291fs-expressing BM cells isolated from Rx291-MDS mice or Rx291/Ezh2^Δ/Δ-MDS mice together with 2 × 10⁵ competitor CD45.1⁺ BM cells. (d) Chimerism of CD45.2⁺GFP⁺ cells in Mac1⁺ myeloid cells, B220⁺ B cells and CD4⁺/CD8⁺ T cells in the PB in Rx291-MDS (n=4) and Rx291/Ezh2^Δ/Δ-MDS recipient mice (n=7) at the advanced MDS stage. Scale bars show mean±s.e.m.