Publication details

Mutated IKZF1 is an independent marker of adverse risk in acute myeloid leukemia

Authors

ECKARDT Jan-Niklas STASIK Sebastian ROELLIG Christoph PETZOLD Andreas SAUER Tim SCHOLL Sebastian HOCHHAUS Andreas CRYSANDT Martina BRUEMMENDORF Tim H NAUMANN Ralph STEFFEN Bjoern KUNZMANN Volker EINSELE Hermann SCHAICH Markus BURCHERT Andreas NEUBAUER Andreas SCHAEFER-ECKART Kerstin SCHLIEMANN Christoph KRAUSE Stefan W HERBST Regina HAENEL Mathias HANOUN Maher KAISER Ulrich KAUFMANN Martin RÁČIL Zdeněk MAYER Jiří OELSCHLAEGEL Uta BERDEL Wolfgang E EHNINGER Gerhard SERVE Hubert MUELLER-TIDOW Carsten PLATZBECKER Uwe BALDUS Claudia D DAHL Andreas SCHETELIG Johannes BORNHAEUSER Martin MIDDEKE Jan Moritz THIEDE Christian

Year of publication 2023
Type Article in Periodical
Magazine / Source Leukemia
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.nature.com/articles/s41375-023-02061-1
Doi http://dx.doi.org/10.1038/s41375-023-02061-1
Keywords Acute myeloid leukaemia; Risk factors
Description Genetic lesions of IKZF1 are frequent events and well-established markers of adverse risk in acute lymphoblastic leukemia. However, their function in the pathophysiology and impact on patient outcome in acute myeloid leukemia (AML) remains elusive. In a multicenter cohort of 1606 newly diagnosed and intensively treated adult AML patients, we found IKZF1 alterations in 45 cases with a mutational hotspot at N159S. AML with mutated IKZF1 was associated with alterations in RUNX1, GATA2, KRAS, KIT, SF3B1, and ETV6, while alterations of NPM1, TET2, FLT3-ITD, and normal karyotypes were less frequent. The clinical phenotype of IKZF1-mutated AML was dominated by anemia and thrombocytopenia. In both univariable and multivariable analyses adjusting for age, de novo and secondary AML, and ELN2022 risk categories, we found mutated IKZF1 to be an independent marker of adverse risk regarding complete remission rate, event-free, relapse-free, and overall survival. The deleterious effects of mutated IKZF1 also prevailed in patients who underwent allogeneic hematopoietic stem cell transplantation (n = 519) in both univariable and multivariable models. These dismal outcomes are only partially explained by the hotspot mutation N159S. Our findings suggest a role for IKZF1 mutation status in AML risk modeling.

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