Identification of the Characteristics and Prognostic Impact of t(3;5)(q25;q35)/NPM1::MLF1 Fusion Genes and NPM1 Mutations in Acute Myeloid Leukemia Patients.

BACKGROUND: NPM1::MLF1/t(3;5)(q25;q35) is a rare non-random genetic abnormality appearing in less than 0.5% of acute myeloid leukemia (AML) cases. Previous research has suggested that the NPM1 fusion gene has biological traits with NPM1 mutations. Meanwhile, there is still controversy over the classification of risk levels of AML with NPM1::MLF1. AIMS: To investigate the clinical features and prognostic significance of this subtype and NPM1 mutations in patients with AML. METHODS: To construct the cohort, we sourced patients from the Database and literatures from 1985 to 2025. Baseline clinical and laboratory characteristics of this group were compared with those of a reference cohort consisting of 643 AML patients and a subset of 46 AML patients with NPM1 mutations, all of whom were treated at our institution. RESULTS: AML patients with NPM1::MLF1 and NPM1 mutations showed statistically significant differences in age of onset, FAB typing, treatment and prognosis. Pediatric patients with NPM1::MLF1 were mainly concentrated in FAB M2 type, demonstrating high remission and low recurrence rates. While adult patients who are concentrated in the FAB M6 type, were mostly young men with high remission and high recurrence rates differ from pediatric patients . Age (> 50)may constitute a risk factor, whereas hematopoietic stem cell transplantation (HSCT) could serve as a protective factor against the high relapse rate. CONCLUSIONS: We identified NPM1::MLF1 as a detrimental risk factor and NPM1 mutations as a favorable risk factor in adults, as their survival rates differ significantly. Reducing the recurrence rate and developing treatment strategies for patients ineligible for HSCT continues to be a challenge.