Figure 2.

Tet2 and Dnmt3a Loss of Function Divergently Influence Rate of Transformation from Same Co-operating Mutation

(A) Kaplan-Meier plot comparing time to morbidity between Control^Vav (n = 30), Flt3^ITD (n = 20), Dnmt3a-KO^Vav (n = 15), Tet2-KO^Vav (n = 11), Dnmt3a-KO^VavFlt3^ITD (n = 16), and Tet2-KO^VavFlt3^ITD (n = 12) mice.

(B) White blood cell count of day 600 Control^Vav and moribund mice of indicated genotypes.

(C) Pathological diagnosis of moribund mice.

(D) Representative flow cytometry plots of moribund mice demonstrating expansion of MPP3 (red box) and depletion of HSCs (purple box) in Flt3^ITD genotypes.

(E) Frequency and number of HSCs and MPP3 in moribund mice.

(F–J) (F) Frequency and number of HSCs and MPP3 in 8-week-old Control^Vav (n = 18), Flt3^ITD (n = 14), Dnmt3a-KO^Vav (n = 18), Dnmt3a-KO^VavFlt3^ITD (n = 10), Tet2-KO^Vav (n = 15), and Tet2-KO^VavFlt3^ITD (n = 9) mice. Pathological analysis of young adult mice showing (G) WBC counts, (H) peripheral blood myeloid cells, (I) spleen weights, and (J) spleen myeloid cells. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.001. Mean ± SEM is shown.