Differential prognostic impact of myelodysplasia-related gene mutations in a European cohort of 4978 intensively treated AML patients

In the European LeukemiaNet (ELN) 2022 recommendations, myelodysplasia-related (MR) gene mutations were classified as a novel adverse prognostic category for intensively treated acute myeloid leukemia (AML). To assess the prognostic impact of individual MR genes within the ELN, clinical, cytogenetic, and molecular data from 4,978 intensively treated AML patients were analyzed. Remission rates and survival outcomes were evaluated. For analyses in context of ELN2022 classification, patients carrying an MR mutation were excluded from the adverse group and analyzed separately; those with co-occurring favorable or intermediate features remained in their respective groups. Overall, 1698 patients (34.1%) harbored at least one MR mutation. Lower complete remission rates were observed in MR-mutated cases (65.7% vs 77.7%; p < 0.001) along with shorter event-free (HR 1.45; p < 0.001), relapse-free (HR 1.33; p < 0.001), and overall survival (HR 1.45; p < 0.001) were recorded. Gene-specific prognostic patterns emerged: ASXL1, RUNX1, SF3B1, and U2AF1 mutations associated with adverse risk-like outcomes; SRSF2 and STAG2 aligned with intermediate-risk; BCOR, EZH2, and ZRSR2 did not differ significantly from intermediate or adverse risk. These findings from a large cooperative cohort highlight prognostic heterogeneity among MR mutations and suggest that SRSF2 and STAG2 mutations are associated with less adverse risk patterns, comparable to intermediate-risk.

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Journal
Leukemia
Published
2025-10-27
DOI
https://doi.org/10.1038/s41375-025-02781-6
Citations
3
Primary Topic
Acute Myeloid Leukemia Research
Type
article
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5.31
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article

Differential prognostic impact of myelodysplasia-related gene mutations in a European cohort of 4978 intensively treated AML patients

Christian Rausch, Arnaud Pigneux, Johannes Schetelig, Éric Delabesse et al.
3 citations
Leukemia
Acute Myeloid Leukemia Research
5.31
article

Differential prognostic impact of myelodysplasia-related gene mutations in a European cohort of 4978 intensively treated AML patients

Christian Rausch, Arnaud Pigneux, Johannes Schetelig, Éric Delabesse, Cristina Sauerland, Christian Récher, Karsten Spiekermann, Arnold Ganser, Sebastian Stasik, Hermann Einsele, Marius Bill, Pierre‐Yves Dumas, Utz Krug, Sebastian Scholl, Tim H. Brümmendorf, Wolfgang E. Berdel, Björn Steffen, Christoph Röllig, Martin Bornhäuser, Klaus Hans Metzeler, Jan‐Niklas Eckardt, Carsten Müller‐Tidow, Maximilian Alexander Röhnert, J Válka, Kerstin Schäfer-Eckart, Claudia Dorothea Baldus, Andreas Hochhaus, Sarah Bertoli, Jan Moritz Middeke, Lars Bullinger, Ulf Schnetzke, Dennis Görlich, Andreas Neubauer, Michael Heuser, Konstanze Döhner, Jiřı́ Mayer, Barbora Weinbergerová, Felicitas Thol, Mathias Hänel, Bernhard J. Woermann, Lars R. Fransecky, Christoph Schliemann, Jan Braess, Andreas Burchert, Maher Hanoun, Uwe Platzbecker, Stefan W. Krause, Tobias Herold, Hubert Serve, Tim Sauer, Martina Crysandt, Martin Kaufmann, Alexander Arthur Wurm, Jiří Šrámek, Wolfgang Hiddemann, Hartmut Döhner, Christian Thiede
article en
3 citations

Abstract

In the European LeukemiaNet (ELN) 2022 recommendations, myelodysplasia-related (MR) gene mutations were classified as a novel adverse prognostic category for intensively treated acute myeloid leukemia (AML). To assess the prognostic impact of individual MR genes within the ELN, clinical, cytogenetic, and molecular data from 4,978 intensively treated AML patients were analyzed. Remission rates and survival outcomes were evaluated. For analyses in context of ELN2022 classification, patients carrying an MR mutation were excluded from the adverse group and analyzed separately; those with co-occurring favorable or intermediate features remained in their respective groups. Overall, 1698 patients (34.1%) harbored at least one MR mutation. Lower complete remission rates were observed in MR-mutated cases (65.7% vs 77.7%; p < 0.001) along with shorter event-free (HR 1.45; p < 0.001), relapse-free (HR 1.33; p < 0.001), and overall survival (HR 1.45; p < 0.001) were recorded. Gene-specific prognostic patterns emerged: ASXL1, RUNX1, SF3B1, and U2AF1 mutations associated with adverse risk-like outcomes; SRSF2 and STAG2 aligned with intermediate-risk; BCOR, EZH2, and ZRSR2 did not differ significantly from intermediate or adverse risk. These findings from a large cooperative cohort highlight prognostic heterogeneity among MR mutations and suggest that SRSF2 and STAG2 mutations are associated with less adverse risk patterns, comparable to intermediate-risk.

LeukemiaVol. 40(1)
Goethe University Frankfurt (DE), Philipps University of Marburg (DE), German Cancer Research Center (DE), Charles University (CZ), Masaryk University (CZ), Heidelberg University (DE), University of Münster (DE), University Hospital Heidelberg (DE), Robert Bosch Hospital (DE), Centre Hospitalier Universitaire de Toulouse (FR), München Klinik Bogenhausen (DE), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), Universitätsklinikum Erlangen (DE), Institute of Haematology and Blood Transfusion (CZ), University Hospital Brno (CZ), German Cancer Society (DE), University Hospital Münster (DE), Paracelsus Medizinische Privatuniversität (DE), Essen University Hospital (DE), Krankenhaus Barmherzige Brüder (DE), University Hospital Leipzig (DE), Universitätsklinikum Würzburg (DE), Stadtwerke Köln (Germany) (DE), University Hospital Frankfurt (DE), Jena University Hospital (DE), Center for Clinical Research (United States) (US), University Hospital in Halle (DE), University Hospital Ulm (DE), University Hospital Carl Gustav Carus (DE), Klinikum Chemnitz (DE), Deutsches Konsortium für Translationale Krebsforschung (DE), Technische Universität Dresden (DE), Ludwig-Maximilians-Universität München (DE), RWTH Aachen University (DE)
Openalex Percentile: Top 4%
Acute Myeloid Leukemia Research
5.31
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