Figure 3. Pre-leukemic HSC bearing DNMT3a^mut generate multilineage engraftment and have a competitive advantage in xenograft repopulation assays.

a, Representative flow cytometric analysis of engrafted human cells harvested from NSG mouse bone marrow (BM) 16 weeks after intrafemoral (i.f.) transplantation of peripheral blood mononuclear cells (PB MNC) from diagnosis and relapse samples of Patient #11. b, Analysis of human graft composition in NSG mouse BM 16 weeks after i.f. transplantation of PB MNC from the diagnosis sample of Patient #11 across a range of cells doses. The percentage of human (CD45+) B (CD19+) and myeloid (CD33+) cells was determined by flow cytometry. Mutant allele frequency (%) in the human graft was determined by droplet digital PCR (ddPCR) analysis of sorted human cells. The length of the bars is proportional to the mutant allele frequency (the scale bar under the first column applies to all columns). c, Summary of DNMT3a^mut allele frequency in the human graft from mice analyzed by ddPCR 8 and 16 weeks after transplantation of PB MNC from Patient #11, compared to isolated hematopoietic stem cell/multipotent progenitors (HSC/MPP) from the patient’s PB at diagnosis. *, P<0.05. Bars indicate mean and standard deviation.