Co-mutation landscape and its prognostic impact on newly diagnosed adult patients with NPM1-mutated de novo acute myeloid leukemia

Approximately 25–35% of adult patients with acute myeloid leukemia (AML) carries NPM1 mutation, which generally indicated a favorable outcome in the absence of FLT3-ITD mutation [ 1 ]. NPM1 mutations are absent in clonal hematopoiesis, and have been considered as AML initiating lesions [ 2 ]. Research on co-mutation characteristics of NPM1 -mutated patients concentrated on FLT3-ITD , which has been suggested to hold a negative prognostic impact on NPM1 -mutated patients by several large retrospective clinical studies [ 3 , 4 ]. Besides FLT3-ITD , although there remains controversy, other high-frequency co-mutations such as DNMT3A , IDH1 , IDH2 , FLT3-TKD , NRAS , and WT1 mutations have also been pointed out to affect the prognosis of NPM1- mutated patients [ 3 , 5 , 6 , 7 , 8 , 9 ]. Indeed, identification of specific co-mutation combinations other than FLT3-ITD mutation is essential for precise risk stratification and treatment strategy optimization for NPM1 -mutated AML patients. Since allogeneic hematopoietic stem cell transplantation (allo-HSCT) is generally considered to improve the long-term outcome of most adverse-risk and suitable intermediate-risk AML patients, for NPM1 -mutated AML patients, it is imperative to revisit the co-mutation profiles to determine the optimal population who may benefit from allo-HSCT.