Fig. 1: Dismal survival of mice with both p53 knock-out and FLT3-ITD knock-in mutations.

a Genotyping analyses of p53 knockout and FLT3-ITD knock-in by PCR. The genotypes of offspring were detected by PCR amplification of p53 or FLT3-ITD mutations in genomic DNA. Moreover, p53 haploinsufficient (p53^+/−) mice (n = 3) showed a 1.8-fold (1.4–2.2-fold) reduction in p53 mRNA expression quantitative PCR assay, while p53 expression was completely absent in p53^−/− mice (n = 3) by the TaqMan assay. Mouse #361 = FLT3-ITD heterozygote, #1436 = ITD/ITD, #1381 = p53^+/−, #1376 and #1348 = ITD/ITD; p53^+/−, #1352 = ITD/ITD; p53^−/−, #1345 = p53^−/−. ITD/ITD = homozygous FLT3-ITD knock-in mice; p53^+/− = heterozygous p53 knock-out mice; p53^−/− = homozygous p53 knock-out mice; ITD/ITD; p53^+/− =mice with homozygous FLT3-ITD knock-in and heterozygous p53 knock-out; ITD/ITD; p53^−/− = mice with homozygous FLT3-ITD knock-in and homozygous p53 knock-out. b Survival curve of WT (wild-type), ITD/ITD; p53^+/−, and ITD/ITD; p53^+/− mice. ***p < 0.001, ****p < 0.0001. c Survival curve of p53^−/− and ITD/ITD; p53^−/− mice. *p < 0.05. d Change in the disease spectrum by cooperation of FLT3-ITD and p53 KO. All except three animals (not classifiable) from the survival curves (b, c) were included. Mice with biclonal disease (the coexistence of AML and ALL/lymphoma) were included in the AML group. In the p53^+/− group, one mouse developed both a solid tumor and lymphoma and was included in the solid tumor subgroup. One p53^−/− mouse developed mixed-phenotype acute leukemia and was included in the ALL/lymphoma subgroup. ALL /lymphoma = almost all are lymphoblastic lymphoma, others = histocytic sarcoma, adenoma/cystic diseases and few animals without pathological abnormality, although termination criteria were met.