Clonal architecture is dynamic and selectively affected by therapy. Proportion of mutated clones in the indicated peripheral blood (A) or BM (B-E) CD34+ fractions of matched samples from untreated (A) or treated (B-E) patients. Mutated genes are indicated in their inferred order of apparition from top to bottom (see Table 1 for details). (A) UPN #516: TET2 K450×, NRAS G12D. (B,D) UPN #507: TET2 S716×, CBL W408R, SRSF2 P95H. C. UPN #550: TET2 D1242TfsX11, RUNX1 Y376LfsX197, SRSF2 P95H, ASXL1 E635RfsX15.(E) UPN #632: TET2 N1156I; NRAS A59G; SRSF2 P95H. The total number of interrogated clones is indicated on the top of the bars. Missing fractions represent phenotypes underrepresented in posttreatment samples. Note that in UPN #632, showing RAEB-2 rapidly evolving to AML at relapse, the LMPP and GMP fractions were dominant, as previously described.47 12 mo, 12 months untreated evolution; ASCT, Allogeneic Stem Cell Transplantation; ESA, Erythropoiesis-Stimulating Agent; HMA, Hypomethylating Agent; HY, Hydroxyurea; IC, Intensive Chemotherapy; LMPP, Lymphoid-primed multipotent progenitors; Re, AML Relapse.
