Response of Tet2−/− Flt3ITD leukemia model to 5-Aza therapy.

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Response of Tet2−/− Flt3ITD leukemia model to 5-Aza therapy. Response of Tet2−/− Flt3ITD leukemia model to 5-Aza therapy. Tet2−/−Flt3ITD leukemia BM transplant model mice were treated with vehicle (veh; n = 5) or 5-Aza (n = 5) therapy. A, Histology of treatment response in liver, BM, and spleen, infiltrating leukemic cells (red arrowhead), megakaryocytes (green arrowheads). B–F, Response to treatment in (B) WBC and spleen weight, (C) peripheral blood (PB) smears, (D) platelet, hematocrit, and PB Mac1−cKit+ population, (E) BM stem cell differentiation with the percentage of multipotent progenitors (MPP, CD48+ CD150− gated on LSK, lin−Sca+ cKit+), and (F) BM erythroid differentiation with the percentage of CD71+Ter119+ erythroid progenitors; WT, representative wild-type sample. Graphs and numbers indicate mean ± SEM. G, WBC of mice following treatment with cycles of 5-Aza (n = 5), holding of therapy (arrow), and resumption of 5-Aza. H, Graph of ERRBS analysis comparing vehicle (n = 4) and 5-Aza treatment (n = 4), indicating proportion of hypomethylated, unchanged, and hypermethylated differentiated methylated cytosines (DMC). I, Graph of overall genomic methylation proportion comparing WT LSKs to Tet2−/−Flt3ITD vehicle (green) and 5-Aza (red) treated LSKs. **, P < 0.01; *, P < 0.05 by the t test. Alan H. Shih et al. Cancer Discov 2017;7:494-505 ©2017 by American Association for Cancer Research