Differential prognostic impact of myelodysplasia-related gene mutations in a European cohort of 4978 intensively treated AML patients
Year: 2025
Type: article
Study design: Observational Study
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.
Source: Leukemia
Authors: Marius Bill, Jan-Niklas Eckardt, Konstanze Döhner, Maximillian-Alexander Röhnert, Christian Rausch, Klaus H. Metzeler, Karsten Spiekermann, Sebastian Stasik, Alexander A. Wurm, Tim Sauer, Sebastian Scholl, Ulf Schnetzke, Andreas Hochhaus, Martina Crysandt, Tim H. Brümmendorf, Utz Krug, Bernhard Wörmann, Hermann Einsele, Wolfgang Hiddemann, Dennis Görlich, Cristina Sauerland, Björn Steffen, Andreas Neubauer, Andreas Burchert, Kerstin Schäfer-Eckart, Wolfgang E. Berdel, Christoph Schliemann, Stefan W. Krause, Mathias Hänel, Maher Hanoun, Martin Kaufmann, Lars Fransecky, Jan Braess, Johannes Schetelig, Jan Moritz Middeke, Lars Bullinger, Michael Heuser, Felicitas Thol, Hubert Serve, Claudia D. Baldus, Uwe Platzbecker, Carsten Müller-Tidow, Jan Válka, Jiří Šrámek, Barbora Weinbergerova, Jiri Mayer, Pierre-Yves Dumas, Sarah Bertoli, Eric Delabesse, Christian Récher, Arnaud Pigneux, Tobias Herold, Arnold Ganser, Hartmut Döhner, Martin Bornhäuser, Christian Thiede, Christoph Röllig
Institutions: University Hospital Carl Gustav Carus, Nationales Centrum für Tumorerkrankungen Dresden, German Cancer Consortium (DKTK) Dresden, Technische Universität Dresden, Universität Ulm, University Hospital Ulm, LMU Klinikum, Ludwig-Maximilians-Universität München, University Hospital Leipzig, German Cancer Research Center, University Hospital Heidelberg, Jena University Hospital, Universitätsklinikum Aachen, RWTH Aachen University, Deutsche Knochenmarkspenderdatei, Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, University of Würzburg, Universitätsklinikum Würzburg, University of Münster, University Hospital Frankfurt, Philipps University of Marburg, Paracelsus Medical University, Nuremberg Hospital, Paracelsus Medizinische Privatuniversität, University Hospital Münster, Universitätsklinikum Erlangen, Klinikum Chemnitz, Essen University Hospital, Robert Bosch Hospital, University Hospital Schleswig-Holstein, Krankenhaus Barmherzige Brüder, Medizinische Hochschule Hannover, University Hospital in Halle, Institute of Haematology and Blood Transfusion, Charles University, University Hospital Plzen, Masaryk University, University Hospital Brno, Centre Hospitalier Universitaire de Bordeaux, Centre Hospitalier Universitaire de Toulouse, Institut universitaire du cancer de Toulouse Oncopole, Université de Toulouse, München Klinik Bogenhausen, München Klinik
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,190
OpenAlex ID: W4415648749