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

J 2023

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

ECKARDT, Jan-Niklas, Sebastian STASIK, Christoph ROELLIG, Andreas PETZOLD, Tim SAUER et. al.

Basic information

Original name

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

Authors

ECKARDT, Jan-Niklas, Sebastian STASIK, Christoph ROELLIG, Andreas PETZOLD, Tim SAUER, Sebastian SCHOLL, Andreas HOCHHAUS, Martina CRYSANDT, Tim H BRUEMMENDORF, Ralph NAUMANN, Bjoern STEFFEN, Volker KUNZMANN, Hermann EINSELE, Markus SCHAICH, Andreas BURCHERT, Andreas NEUBAUER, Kerstin SCHAEFER-ECKART, Christoph SCHLIEMANN, Stefan W KRAUSE, Regina HERBST, Mathias HAENEL, Maher HANOUN, Ulrich KAISER, Martin KAUFMANN, Zdeněk RÁČIL (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Uta OELSCHLAEGEL, Wolfgang E BERDEL, Gerhard EHNINGER, Hubert SERVE, Carsten MUELLER-TIDOW, Uwe PLATZBECKER, Claudia D BALDUS, Andreas DAHL, Johannes SCHETELIG, Martin BORNHAEUSER, Jan Moritz MIDDEKE and Christian THIEDE

Edition

Leukemia, London, Nature Publishing Group, 2023, 0887-6924

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 11.400 in 2022

RIV identification code

RIV/00216224:14110/23:00132558

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/s41375-023-02061-1

UT WoS

001085283400001

Keywords in English

Acute myeloid leukaemia; Risk factors

Abstract

V originále

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.

Citovat

ECKARDT, Jan-Niklas, Sebastian STASIK, Christoph ROELLIG, Andreas PETZOLD, Tim SAUER, Sebastian SCHOLL, Andreas HOCHHAUS, Martina CRYSANDT, Tim H BRUEMMENDORF, Ralph NAUMANN, Bjoern STEFFEN, Volker KUNZMANN, Hermann EINSELE, Markus SCHAICH, Andreas BURCHERT, Andreas NEUBAUER, Kerstin SCHAEFER-ECKART, Christoph SCHLIEMANN, Stefan W KRAUSE, Regina HERBST, Mathias HAENEL, Maher HANOUN, Ulrich KAISER, Martin KAUFMANN, Zdeněk RÁČIL, Jiří MAYER, Uta OELSCHLAEGEL, Wolfgang E BERDEL, Gerhard EHNINGER, Hubert SERVE, Carsten MUELLER-TIDOW, Uwe PLATZBECKER, Claudia D BALDUS, Andreas DAHL, Johannes SCHETELIG, Martin BORNHAEUSER, Jan Moritz MIDDEKE and Christian THIEDE. Mutated IKZF1 is an independent marker of adverse risk in acute myeloid leukemia. Leukemia. London: Nature Publishing Group, 2023, vol. 37, No 12, p. 2395-2403. ISSN 0887-6924. Available from: https://dx.doi.org/10.1038/s41375-023-02061-1.

@article{2351119,
   author = {Eckardt, JanandNiklas and Stasik, Sebastian and Roellig, Christoph and Petzold, Andreas and Sauer, Tim and Scholl, Sebastian and Hochhaus, Andreas and Crysandt, Martina and Bruemmendorf, Tim H and Naumann, Ralph and Steffen, Bjoern and Kunzmann, Volker and Einsele, Hermann and Schaich, Markus and Burchert, Andreas and Neubauer, Andreas and SchaeferandEckart, Kerstin and Schliemann, Christoph and Krause, Stefan W and Herbst, Regina and Haenel, Mathias and Hanoun, Maher and Kaiser, Ulrich and Kaufmann, Martin and Ráčil, Zdeněk and Mayer, Jiří and Oelschlaegel, Uta and Berdel, Wolfgang E and Ehninger, Gerhard and Serve, Hubert and MuellerandTidow, Carsten and Platzbecker, Uwe and Baldus, Claudia D and Dahl, Andreas and Schetelig, Johannes and Bornhaeuser, Martin and Middeke, Jan Moritz and Thiede, Christian},
   article_location = {London},
   article_number = {12},
   doi = {http://dx.doi.org/10.1038/s41375-023-02061-1},
   keywords = {Acute myeloid leukaemia; Risk factors},
   language = {eng},
   issn = {0887-6924},
   journal = {Leukemia},
   title = {Mutated IKZF1 is an independent marker of adverse risk in acute myeloid leukemia},
   url = {https://www.nature.com/articles/s41375-023-02061-1},
   volume = {37},
   year = {2023}
}

TY  - JOUR
ID  - 2351119
AU  - 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
PY  - 2023
TI  - Mutated IKZF1 is an independent marker of adverse risk in acute myeloid leukemia
JF  - Leukemia
VL  - 37
IS  - 12
SP  - 2395-2403
EP  - 2395-2403
PB  - Nature Publishing Group
SN  - 08876924
KW  - Acute myeloid leukaemia
KW  - Risk factors
UR  - https://www.nature.com/articles/s41375-023-02061-1
N2  - 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.
ER  -

ECKARDT, Jan-Niklas, Sebastian STASIK, Christoph ROELLIG, Andreas PETZOLD, Tim SAUER, Sebastian SCHOLL, Andreas HOCHHAUS, Martina CRYSANDT, Tim H BRUEMMENDORF, Ralph NAUMANN, Bjoern STEFFEN, Volker KUNZMANN, Hermann EINSELE, Markus SCHAICH, Andreas BURCHERT, Andreas NEUBAUER, Kerstin SCHAEFER-ECKART, Christoph SCHLIEMANN, Stefan W KRAUSE, Regina HERBST, Mathias HAENEL, Maher HANOUN, Ulrich KAISER, Martin KAUFMANN, Zdeněk RÁČIL, Jiří MAYER, Uta OELSCHLAEGEL, Wolfgang E BERDEL, Gerhard EHNINGER, Hubert SERVE, Carsten MUELLER-TIDOW, Uwe PLATZBECKER, Claudia D BALDUS, Andreas DAHL, Johannes SCHETELIG, Martin BORNHAEUSER, Jan Moritz MIDDEKE and Christian THIEDE. Mutated IKZF1 is an independent marker of adverse risk in acute myeloid leukemia. \textit{Leukemia}. London: Nature Publishing Group, 2023, vol.~37, No~12, p.~2395-2403. ISSN~0887-6924. Available from: https://dx.doi.org/10.1038/s41375-023-02061-1.

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