Fig. 3: Cdx2 synergizes with Flt3-ITD to accelerate myeloproliferation.

a Diagram of breeding strategy to produce Scl:Cdx2/Flt3ITD/+ mice. LSL-Cdx2-mCherry mice were crossed with Flt3ITD/+ germline mutant mice that were previously crossed with Scl-CreERT transgene mice (Scl-cre/Flt3ITD/+). Unexcised Scl:Cdx2/Flt3ITD/+ mice are fed tamoxifen-loaded chow for two weeks. b Survival curve of tamoxifen-treated mice (Scl-CreERT n = 18; Scl:Cdx2 n = 22; Scl/Flt3ITD/+ n = 16; Scl:Cdx2/Flt3ITD/+ n = 21). c PB leukocytes (WBC), d hemoglobin and e platelet counts of mice, and (f) spleen size relative to body mass of mice at sacrifice (Flt3ITD/+ n = 7; Scl/Flt3ITD/+ n = 7; Scl:Cdx2/Flt3ITD/+ n = 19). g Frequency of B220-positive B cells, CD3-positive T cells and Gr1-positive myeloid cells in PB of mice at sacrifice (Scl-cre n = 9; Scl:Cdx2 n = 14; Scl/Flt3ITD/+ n = 8; Scl:Cdx2/Flt3ITD/+ n = 13). h Representative Wright-Giemsa stained smear of Scl/Flt3ITD/+ PB with mild granulopoiesis and Scl:Cdx2/Flt3ITD/+ PB showing monocytosis and hypersegmented neutrophils resulting in MPN (observed in multiple independent animals). Scale bars on bottom left of each image indicate 10 µm. N = biologically independent animals. Statistical analyses performed using two-tailed Mann–Whitney test. Log-rank Mantel-Cox test used for survival curve. Data are plotted as mean values +/− SD. n.s.; not significant. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.