Differential prognostic impact of myelodysplasia-related gene mutations in a European cohort of 4978 intensively treated AML patients
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BILL, Marius; Jan-Niklas ECKARDT; Konstanze DOHNER; Maximillian-Alexander ROHNERT; Christian RAUSCH; Klaus H METZELER; Karsten SPIEKERMANN; Sebastian STASIK; Alexander A WURM; Tim SAUER; Sebastian SCHOLL; Ulf SCHNETZKE; Andreas HOCHHAUS; Martina CRYSANDT; Tim H BRUMMENDORF; Utz KRUG; Bernhard WORMANN; Hermann EINSELE; Wolfgang HIDDEMANN; Dennis GORLICH; Cristina SAUERLAND; Bjorn STEFFEN; Andreas NEUBAUER; Andreas BURCHERT; Kerstin SCHAFER-ECKART; Wolfgang E BERDEL; Christoph SCHLIEMANN; Stefan W KRAUSE; Mathias HANEL; 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 MULLER-TIDOW; Jan VALKA; Jiri SRAMEK; Barbora WEINBERGEROVÁ; Jiří MAYER; Pierre-Yves DUMAS; Sarah BERTOLI; Eric DELABESSE; Christian RECHER; Arnaud PIGNEUX; Tobias HEROLD; Arnold GANSER; Hartmut DOHNER; Martin BORNHAUSER; Christian THIEDE a Christoph ROLLIG
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.
BILL, Marius; Jan-Niklas ECKARDT; Konstanze DOHNER; Maximillian-Alexander ROHNERT; Christian RAUSCH; Klaus H METZELER; Karsten SPIEKERMANN; Sebastian STASIK; Alexander A WURM; Tim SAUER; Sebastian SCHOLL; Ulf SCHNETZKE; Andreas HOCHHAUS; Martina CRYSANDT; Tim H BRUMMENDORF; Utz KRUG; Bernhard WORMANN; Hermann EINSELE; Wolfgang HIDDEMANN; Dennis GORLICH; Cristina SAUERLAND; Bjorn STEFFEN; Andreas NEUBAUER; Andreas BURCHERT; Kerstin SCHAFER-ECKART; Wolfgang E BERDEL; Christoph SCHLIEMANN; Stefan W KRAUSE; Mathias HANEL; 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 MULLER-TIDOW; Jan VALKA; Jiri SRAMEK; Barbora WEINBERGEROVÁ; Jiří MAYER; Pierre-Yves DUMAS; Sarah BERTOLI; Eric DELABESSE; Christian RECHER; Arnaud PIGNEUX; Tobias HEROLD; Arnold GANSER; Hartmut DOHNER; Martin BORNHAUSER; Christian THIEDE a Christoph ROLLIG. Differential prognostic impact of myelodysplasia-related gene mutations in a European cohort of 4978 intensively treated AML patients. Leukemia. LONDON: SPRINGERNATURE, 2026, roč. 40, č. 1, s. 63-71. ISSN 0887-6924. Dostupné z: https://doi.org/10.1038/s41375-025-02781-6.
@article{2537907, author = {Bill, Marius and Eckardt, JanandNiklas and Dohner, Konstanze and Rohnert, MaximillianandAlexander and Rausch, Christian and Metzeler, Klaus H and Spiekermann, Karsten and Stasik, Sebastian and Wurm, Alexander A and Sauer, Tim and Scholl, Sebastian and Schnetzke, Ulf and Hochhaus, Andreas and Crysandt, Martina and Brummendorf, Tim H and Krug, Utz and Wormann, Bernhard and Einsele, Hermann and Hiddemann, Wolfgang and Gorlich, Dennis and Sauerland, Cristina and Steffen, Bjorn and Neubauer, Andreas and Burchert, Andreas and SchaferandEckart, Kerstin and Berdel, Wolfgang E and Schliemann, Christoph and Krause, Stefan W and Hanel, Mathias and Hanoun, Maher and Kaufmann, Martin and Fransecky, Lars and Braess, Jan and Schetelig, Johannes and Middeke, Jan Moritz and Bullinger, Lars and Heuser, Michael and Thol, Felicitas and Serve, Hubert and Baldus, Claudia D and Platzbecker, Uwe and MullerandTidow, Carsten and Valka, Jan and Sramek, Jiri and Weinbergerová, Barbora and Mayer, Jiří and Dumas, PierreandYves and Bertoli, Sarah and Delabesse, Eric and Recher, Christian and Pigneux, Arnaud and Herold, Tobias and Ganser, Arnold and Dohner, Hartmut and Bornhauser, Martin and Thiede, Christian and Rollig, Christoph}, article_location = {LONDON}, article_number = {1}, doi = {https://doi.org/10.1038/s41375-025-02781-6}, keywords = {acute myeloid leukemia; myelodysplasia-related mutations; prognostic impact; intensive chemotherapy; European cohort}, language = {eng}, issn = {0887-6924}, journal = {Leukemia}, title = {Differential prognostic impact of myelodysplasia-related gene mutations in a European cohort of 4978 intensively treated AML patients}, url = {https://www.nature.com/articles/s41375-025-02781-6}, volume = {40}, year = {2026} }
TY - JOUR ID - 2537907 AU - Bill, Marius - Eckardt, Jan-Niklas - Dohner, Konstanze - Rohnert, Maximillian-Alexander - Rausch, Christian - Metzeler, Klaus H - Spiekermann, Karsten - Stasik, Sebastian - Wurm, Alexander A - Sauer, Tim - Scholl, Sebastian - Schnetzke, Ulf - Hochhaus, Andreas - Crysandt, Martina - Brummendorf, Tim H - Krug, Utz - Wormann, Bernhard - Einsele, Hermann - Hiddemann, Wolfgang - Gorlich, Dennis - Sauerland, Cristina - Steffen, Bjorn - Neubauer, Andreas - Burchert, Andreas - Schafer-Eckart, Kerstin - Berdel, Wolfgang E - Schliemann, Christoph - Krause, Stefan W - Hanel, Mathias - Hanoun, Maher - Kaufmann, Martin - Fransecky, Lars - Braess, Jan - Schetelig, Johannes - Middeke, Jan Moritz - Bullinger, Lars - Heuser, Michael - Thol, Felicitas - Serve, Hubert - Baldus, Claudia D - Platzbecker, Uwe - Muller-Tidow, Carsten - Valka, Jan - Sramek, Jiri - Weinbergerová, Barbora - Mayer, Jiří - Dumas, Pierre-Yves - Bertoli, Sarah - Delabesse, Eric - Recher, Christian - Pigneux, Arnaud - Herold, Tobias - Ganser, Arnold - Dohner, Hartmut - Bornhauser, Martin - Thiede, Christian - Rollig, Christoph PY - 2026 TI - Differential prognostic impact of myelodysplasia-related gene mutations in a European cohort of 4978 intensively treated AML patients JF - Leukemia VL - 40 IS - 1 SP - 63-71 EP - 63-71 PB - SPRINGERNATURE SN - 08876924 KW - acute myeloid leukemia KW - myelodysplasia-related mutations KW - prognostic impact KW - intensive chemotherapy KW - European cohort UR - https://www.nature.com/articles/s41375-025-02781-6 N2 - 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. ER -
BILL, Marius; Jan-Niklas ECKARDT; Konstanze DOHNER; Maximillian-Alexander ROHNERT; Christian RAUSCH; Klaus H METZELER; Karsten SPIEKERMANN; Sebastian STASIK; Alexander A WURM; Tim SAUER; Sebastian SCHOLL; Ulf SCHNETZKE; Andreas HOCHHAUS; Martina CRYSANDT; Tim H BRUMMENDORF; Utz KRUG; Bernhard WORMANN; Hermann EINSELE; Wolfgang HIDDEMANN; Dennis GORLICH; Cristina SAUERLAND; Bjorn STEFFEN; Andreas NEUBAUER; Andreas BURCHERT; Kerstin SCHAFER-ECKART; Wolfgang E BERDEL; Christoph SCHLIEMANN; Stefan W KRAUSE; Mathias HANEL; 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 MULLER-TIDOW; Jan VALKA; Jiri SRAMEK; Barbora WEINBERGEROVÁ; Jiří MAYER; Pierre-Yves DUMAS; Sarah BERTOLI; Eric DELABESSE; Christian RECHER; Arnaud PIGNEUX; Tobias HEROLD; Arnold GANSER; Hartmut DOHNER; Martin BORNHAUSER; Christian THIEDE a Christoph ROLLIG. Differential prognostic impact of myelodysplasia-related gene mutations in a European cohort of 4978 intensively treated AML patients. \textit{Leukemia}. LONDON: SPRINGERNATURE, 2026, roč.~40, č.~1, s.~63-71. ISSN~0887-6924. Dostupné z: https://doi.org/10.1038/s41375-025-02781-6.