Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients

Acute myeloid leukemia (AML) patients with various nucleophosmin 1 (NPM1) mutations are controversial in the prognosis. This study aimed to investigate the prognosis of patients according to types of NPM1 mutations (NPM1^mut).

Bone marrow samples of 528 patients newly diagnosed with AML, were collected for morphology, immunology, cytogenetics, and molecular biology examinations. Gene mutations were detected by next-generation sequencing (NGS) technology.

About 25.2% of cases exhibited NPM1^mut. 83.5% of cases were type A, while type B and D were respectively account for 2.3% and 3.0%. Furthermore, 15 cases of rare types were identified, of which 2 cases have not been reported. Clinical characteristics were similar between patients with A-type NPM1 mutations (NPM1^{A - type mut}) and non-A-type NPM1 mutations (NPM1^{non - A-type mut}). Event-free survival (EFS) was significantly different between patients with low NPM1^{non - A-type mut} variant allele frequency (VAF) and low NPM1^{A - type mut} VAF (median EFS = 3.9 vs. 8.5 months, P = 0.020). The median overall survival (OS) of the NPM1^{non - A-type mut}FLT3-ITD^mut group, the NPM1^{A - type mut}FLT3-ITD^mut group, the NPM1^{non - A-type mut}FLT3-ITD^wt group, and the NPM1^{A - type mut}FLT3-ITD^wt group were 3.9, 10.7, 17.3 and 18.8 months, while the median EFS of the corresponding groups was 1.4, 5.0, 7.6 and 9.2 months (P < 0.0001 and P = 0.004, respectively).

No significant difference was observed in OS and EFS between patients with NPM1^{A - type mut} and NPM1^{non - A-type mut}. However, types of NPM1 mutations and the status of FLT3-ITD mutations may jointly have an impact on the prognosis of AML patients.