# Prognostic impact of myelodysplasia-related gene mutations in ELN-2022 favorable-risk acute myeloid leukemia subtypes

## TL;DR

This study examines how myelodysplasia-related gene mutations affect outcomes in patients with favorable-risk acute myeloid leukemia.

## Contribution

The study identifies that a high mutation burden of myelodysplasia-related genes, not single mutations, is linked to worse survival in favorable-risk AML.

## Key findings

- Patients with two or more myelodysplasia-related gene mutations had significantly poorer leukemia-free survival.
- A single myelodysplasia-related gene mutation did not significantly impact overall or leukemia-free survival.
- Higher mutation burden of myelodysplasia-related genes is independently associated with worse leukemia-free survival.

## Abstract

The 2022 European Leukemia Net (ELN) risk stratification categorizes acute myeloid leukemia (AML) with myelodysplasia-related gene (MRG) mutations - including ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 and/or ZRSR2 - as “adverse-risk”. However, the prognostic relevance of MRG mutations in patients with favorable-risk AML remains uncertain.

In this study, we analyzed a cohort of 221 adult patients with de novo favorable-risk AML. Risk groups were classified according to the 2022 European Leukemia Net guideline.

A total of 47 AML patients (21.3%) harbored MRG mutations. The presence of MRG mutations was associated with older age (57 vs. 49, p = 0.005), lower white blood cell count (6.9 vs. 14.5, p = 0.015), and the presence of TET2 (27.7% vs. 10.9%, p = 0.004), MPL (6.4% vs. 0.6%, p = 0.031), and ETV6 (6.4% vs. 1.1%, p = 0.066) mutations. Our findings indicated that the presence of MRG mutations did not significantly impact 2-year overall survival (OS) (75.2% vs. 69.4%, p = 0.285) or leukemia-free survival (LFS) (58.9% vs. 52.5%, p = 0.640). However, patients with two or more MRG mutations had significantly poorer LFS than those with one MRG mutation (p = 0.004) or without MRG mutations (p = 0.001). By multivariable analysis, ≥2 MRG mutations was independently associated with worse LFS.

The presence of a single MRG mutation did not confer a worse prognosis in favorable-risk AML, whereas a high MRG mutation burden (≥2 mutations) was independently associated with poorer LFS. This study suggests that quantifying the MRG mutation burden may inform risk stratification in this patient population.