Figure 5.
c-Myc haploinsufficiency rescues Apc-heterozygous deletion-induced anemia. (A) Kaplan-Meier survival curve of WT (Apcfl/+c-Mycfl/+), Apc+/− (A, Apcfl/+ Mx1Cre), Apc+/−c-Myc+/− (AC, Apcfl/+c-Mycfl/+ Mx1Cre), and c-Myc+/−(C, c-Mycfl/+ Mx1Cre) mice (n = 6-9). The graph starts from the first day after the third pIpC injection. (B-E) Absolute number of RBCs (B), Hb level (C), mean corpuscular volume (MCV) (D), and RBC distribution width (RDW) (E) in PB in each group of mice (n = 6-9). Data were collected when the first Apc+/− mice become moribund. (F-G) Flow cytometric analysis of erythroid (Ter119+) in spleen (Sp) from WT (Apcfl/+c-Mycfl/+), Apc+/−, Apc+/−c-Myc+/−, and c-Myc+/− mice. Gating strategy (F) and summary data (G) (n = 4). (H) Spleen weights for each cohort (n = 4). (I) Histological analysis of PB smear, spleen touch, and spleen section from WT (Apcfl/+c-Mycfl/+), Apc+/−, and Apc+/−c-Myc+/− mice. PB and spleen touch, May-Grünwald-Giemsa stain; spleen, hematoxylin and eosin. Scale bars, 50 μm. (J) Kaplan-Meier survival curve of WT control, Apc+/−, Apc+/−c-Myc+/−, and c-Myc +/− mice reconstituted with WT CD45.1 BM cells (n = 4-7). The graph starts from the first day after the third pIpC injection. The number of RBCs (K) and Hb level (L) in each cohort of mice from the first to the fourth month after transplantation (n = 4-7). (M) Flow cytometric analysis of erythroid blast cells in spleen from each cohort of mice (n = 4). (N) Kaplan-Meier survival curve of WT and Apc+/− mice reconstituted with WT CD45.1 BM cells after receiving 10 Gy irradiation. WT mice were treated with vehicle control and Apc+/− mice were treated with vehicle control or CX-3543 (n = 5-6). CX-3543 was administered for 3 times every week after 2 months of pIpC-induced deletion until mice were euthanized. The graph starts from the first day after the third pIpC injection. Absolute number of RBCs (O) and the Hb level (P) in WT mice treated with vehicle control or Apc+/− mice treated with vehicle control or CX-3543 (n = 5-6). Data were measured at the time when the first Apc+/− mouse become moribund. *P < .05; **P < .01; ***P < .001, by Student t test or log-rank (Mantel-Cox) test for survival curve.

c-Myc haploinsufficiency rescues Apc-heterozygous deletion-induced anemia. (A) Kaplan-Meier survival curve of WT (Apcfl/+c-Mycfl/+), Apc+/− (A, Apcfl/+ Mx1Cre), Apc+/−c-Myc+/− (AC, Apcfl/+c-Mycfl/+ Mx1Cre), and c-Myc+/−(C, c-Mycfl/+ Mx1Cre) mice (n = 6-9). The graph starts from the first day after the third pIpC injection. (B-E) Absolute number of RBCs (B), Hb level (C), mean corpuscular volume (MCV) (D), and RBC distribution width (RDW) (E) in PB in each group of mice (n = 6-9). Data were collected when the first Apc+/− mice become moribund. (F-G) Flow cytometric analysis of erythroid (Ter119+) in spleen (Sp) from WT (Apcfl/+c-Mycfl/+), Apc+/−, Apc+/−c-Myc+/−, and c-Myc+/− mice. Gating strategy (F) and summary data (G) (n = 4). (H) Spleen weights for each cohort (n = 4). (I) Histological analysis of PB smear, spleen touch, and spleen section from WT (Apcfl/+c-Mycfl/+), Apc+/−, and Apc+/−c-Myc+/− mice. PB and spleen touch, May-Grünwald-Giemsa stain; spleen, hematoxylin and eosin. Scale bars, 50 μm. (J) Kaplan-Meier survival curve of WT control, Apc+/−, Apc+/−c-Myc+/−, and c-Myc +/− mice reconstituted with WT CD45.1 BM cells (n = 4-7). The graph starts from the first day after the third pIpC injection. The number of RBCs (K) and Hb level (L) in each cohort of mice from the first to the fourth month after transplantation (n = 4-7). (M) Flow cytometric analysis of erythroid blast cells in spleen from each cohort of mice (n = 4). (N) Kaplan-Meier survival curve of WT and Apc+/− mice reconstituted with WT CD45.1 BM cells after receiving 10 Gy irradiation. WT mice were treated with vehicle control and Apc+/− mice were treated with vehicle control or CX-3543 (n = 5-6). CX-3543 was administered for 3 times every week after 2 months of pIpC-induced deletion until mice were euthanized. The graph starts from the first day after the third pIpC injection. Absolute number of RBCs (O) and the Hb level (P) in WT mice treated with vehicle control or Apc+/− mice treated with vehicle control or CX-3543 (n = 5-6). Data were measured at the time when the first Apc+/− mouse become moribund. *P < .05; **P < .01; ***P < .001, by Student t test or log-rank (Mantel-Cox) test for survival curve.

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