Pharmacological inhibition of WNT signaling using pyrvinium prevents the development of MDS in Apc^del/+ mice. (A) Mx1-Cre⁻Apc^fl/+ (Cre⁻) or Mx1-Cre⁺Apc^fl/+ (Cre⁺, also referred to as Apc^del/+) were injected IP for 300 days with 0.1 mg/kg PT or vehicle (DMSO) twice per week (beginning when Apc deletion was induced at 2 months of age). Kaplan-Meier survival curves of Cre⁻ and Cre⁺ mice treated with PT or DMSO are shown. DMSO-treated Cre⁺ mice died with a median survival of 227 days. PT-treated Cre⁺ mice did not develop disease as long as PT was administered; however, they slowly developed a severe anemia after PT was withdrawn and survived for a median of 360 days (DMSO 227 days vs PT 360 days; P = .0007). Cre⁻ mice, treated with PT or vehicle, survived until the end of the study indicating no major adverse effects from PT administration. (B) Hb counts from Cre⁻ (open symbols) and Cre⁺ (solid black symbols) mice injected with DMSO (left) or PT (right) over time. Injections were stopped at 35 weeks, after all DMSO-treated Cre⁺ were sacrificed. None of the PT-treated Cre⁺ mice were anemic at 35 weeks (with the exception of mouse 8493, which was mildly anemic with a Hb of ∼10 g/dL). However, following cessation of PT treatment, anemia slowly developed at varying rates in all PT-treated Cre⁺ mice. (C) Spleen size and percentage of CD71⁺Ter119⁺ erythroid cells, Gr1⁺Cd11b⁺ myeloid cells, and CD19⁺IgM⁺ B cells in spleen isolated from DMSO-treated Cre⁻ (450 days) or Cre⁺ (173-248 days) mice or PT-treated Cre⁻ (450 days) or Cre⁺ (304-449 days) mice. After PT cessation, PT-treated Cre⁺ mice eventually developed splenomegaly with marked erythroid proliferation and effacement of B lymphoid cells, indicators of the MDS seen in the DMSO-treated Cre⁺ mice.