Sequential next generation sequencing analysis in homogeneously treated low risk NPM1-mutated acute myeloid leukemia with an adverse clinical outcome

In conclusion, in this small cohort of patients with an adverse clinical outcome, the prevailing pattern of detectability and undetectability of NPM1 mut with stable co-mutations at similar VAFs prompted us to hypothesize that NPM1 mutation can occur very early before the expansion of a dominating preleukemic clonal hematopoiesis, and in this case, clonal hematopoiesis becomes undetectable at remission but persists along with NPM1mut at a deeper level on chemo-resistant leukemic stem cell clones that may drive/be responsible for subsequent relapse.

Therefore, relapse may rely on the persistence of a chemo-resistant leukemic stem cell clone that harbors both pre-leukemic and NPM1 mutations and persists at very low level in the absence of an evident clonal hematopoiesis.