Dynamin2 mutations in newly diagnosed acute myeloid leukemia: clinical characteristics, and prognostic significance

TL;DR

This study finds that mutations in the DNM2 gene are rare in AML but are linked to better survival outcomes, possibly due to co-occurring mutations in CEBPA or RUNX1::RUNX1T1.

Contribution

The study identifies DNM2 mutations as a novel prognostic marker in AML, particularly when co-occurring with CEBPA or RUNX1::RUNX1T1 mutations.

Findings

DNM2 mutations were found in 2% of AML patients, mostly in the dynamin central region.

DNM2 mutations were associated with better overall and event-free survival in AML patients.

DNM2 mutations frequently co-occurred with CEBPA mutations or RUNX1::RUNX1T1 fusion genes.

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous myeloid malignancy which can be classified by genetic aberrations. To evaluate the impact of the dynamin 2 mutation in AML, we systematically assessed the characteristics and prognostic of DNM2 mutated patients in AML. In 912 AML patients, 20 somatic mutations in the DNM2 gene were identified among the 18 DNM2 mutated AML patients (2%). Of the mutation events, 60% (12/20) were in the dynamin central region of DNM2. DNM2mutations were preferentially occurred in AML with CEBPA mutation (11/18, 61.1%), or RUNX1::RUNX1T1 fusion gene (6/18, 33.3%). DNM2 mutations were associated with better overall survival (P = 0.028), event-free survival (P = 0.0093) and trends towards better relapse-free survival (P = 0.08), which seems potentially attribute to its coexisting with CEBPA mutation and RUNX1::RUNX1T1 fusion gene. Our study demonstrated the clinical characteristics and the role of DNM2 mutations in AML, which might facilitate understanding the pathogenesis of AML.

The online version contains supplementary material available at 10.1186/s40164-025-00628-5.

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