WT1mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system

The impact of WT1mutations in acute myeloid leukemia (AML) is not completely settled. We aimed to determine the clinical implication of WT1mutation in 470 de novo non-M3 AML patients and its stability during the clinical course. WT1mutations were identified in 6.8% of total patients and 8.3% of younger patients with normal karyotype (CN-AML). The WT1mutation was closely associated with younger age (P< .001), French-American-British M6 subtype (P= .006), and t(7;11)(p15;p15) (P= .003). Multivariate analysis demonstrated that the WT1mutation was an independent poor prognostic factor for overall survival and relapse-free survival among total patients and the CN-AML group. A scoring system incorporating WT1mutation, NPM1/FLT3-ITD, CEBPAmutations, and age into survival analysis proved to be very useful to stratify CN-AML patients into different prognostic groups (P< .001). Sequential analyses were performed on 133 patients. WT1mutations disappeared at complete remission in all WT1-mutated patients studied. At relapse, 3 of the 16 WT1-mutated patients who had paired samples lost the mutation and 2 acquired additional mutations, whereas 3 of 110 WT1-wild patients acquired novel mutations. In conclusion, WT1mutations are correlated with poor prognosis in AML patients. The mutation status may be changed in some patients during AML progression.