Co-mutation landscape and its prognostic impact on newly diagnosed adult patients with NPM1-mutated de novo acute myeloid leukemia
Yiyi Yao, Yile Zhou, Nanfang Zhuo, Wanzhuo Xie, Haitao Meng, Yinjun Lou, Liping Mao, Hongyan Tong, Jiejing Qian, Min Yang, Wenjuan Yu, De Zhou, Jie Jin, Huafeng Wang
Abstract
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.