Figure 3. MDMX overexpression induces AML in the Tet2−/− MPN/MDS model and Tet2+/− clonal hematopoiesis model.
(A) Schema of the breeding strategy, resultant genotypes and phenotypes. (B) Survival of Tet2−/− and Tet2−/−;Mdmx-Tg mice (n=15 for Tet2−/−, 18 for Tet2−/−;Mdmx-Tg). **: 0.001≤P<0.01 by log-rank test. (C) Abdominal cavity of moribund Tet2−/−;Mdmx-Tg mouse and a Tet2−/− littermate reveals drastic hepatosplenomegaly in the Tet2−/−;Mdmx-Tg mouse. (D) Left: Bone marrow (BM) cytospins of a non-diseased Tet2−/− mouse at 12-months of age (12M), a moribund (MPN/MDS-like) Tet2−/− mouse at 18-months of age (18M), and a moribund (AML) Tet2−/−;Mdmx-Tg mouse at 12M. Right: percentage of blasts in the BM cells of moribund Tet2−/−;Mdmx-Tg and Tet2−/− mice. Bars indicate Mean±SEM. *: 0.01≤P<0.05 by T test. (E) Flow cytometric analysis of BM/spleen cells of a non-diseased Tet2−/− mouse (12M), a moribund (MPN/MDS-like) Tet2−/− mouse (18M), and a moribund (AML) Tet2−/−;Mdmx-Tg mouse (12M). (F) Abdominal cavity of a moribund Tet2+/−;Mdmx-Tg mouse and its littermate (Tet2+/−). (G) BM cytospins of a moribund (AML) Tet2+/−;Mdmx-Tg mouse (15-month-old; 15M) and a Tet2+/− littermate. (H) Flow cytometric analysis of BM and spleen cells of a moribund Tet2+/−;Mdmx-Tg mouse and a Tet2+/− littermate. # (D) (G) Arrows indicate morphological blasts. Scale bars: 40μm.
