Fig. 5. Evolutionary pathways in TP53 mutated acute myeloid leukemia (AML).

A Comparison of TP53 mutation variant allelic frequency (VAF) between immunophenotypic leukemia stem cell (LSC) and non-LSC compartments in 10 AML patients. Gray lines indicate no statistically significant difference, while red lines indicate a significant difference between the two VAFs. B Tables show the VAF of TP53 mutation and percentage of cells with loss of wild type TP53 allele detected by fluorescence in situ hybridization in 4 AML patients for whom the VAF of mutation doubled from LSC to non-LSC compartment. C Schema depicting the evolution of TP53 mutated AML from LSCs through clonal selection and progression. D Graph demonstrates the VAFs for TP53 and TET2 mutations in isolated single colonies arising from immunophenotypic LSCs in patient AML-4. E Graph demonstrates the VAFs for TP53 and TET2 mutations in immunophenotypic hematopoietic stem cell (HSC), LSC and TIM3 + LSCs in patient AML-4. F Immunophenotypically defined HSC, LSC and TIM3 + LSCs were isolated from patient AML-4 and cultured in methylcellulose-based MethoCult medium. Graph shows the number of colonies detected at each time point throughout serial replating. G Schema depicting the clonal evolution of leukemia in patient AML-4. H Graph demonstrates the VAFs for TET2, JAK2, TP53, and GATA2 mutations in immunophenotypically defined HSCs and LSCs in patient AML-43. I Schema depicting the clonal evolution of myeloproliferative neoplasm (MPN) and leukemia in patient AML-43. J LSCs from AML-11 were sorted and injected into NSG mice. After meeting early removal criteria (ERC), mice were sacrificed and bone marrow/spleen cells were harvested to perform LC-FACSeq analysis. K Graph demonstrates the VAFs for TP53 mutation in human CD45⁺, CD34⁺CD38^–, and CD34⁺CD38⁺ compartments of murine AML-11 (murAML-11). L Schema depicting the clonal composition of murAML-11. *p < 0.05, **p < 0.01, ***p < 0.001.