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@ARTICLE{Eckardt:284759,
author = {J.-N. Eckardt and S. Stasik and C. Röllig and A. Petzold
and T. Sauer$^*$ and S. Scholl and A. Hochhaus and M.
Crysandt and T. H. Brümmendorf and R. Naumann and B.
Steffen and V. Kunzmann and H. Einsele and M. Schaich and A.
Burchert and A. Neubauer and K. Schäfer-Eckart and C.
Schliemann and S. W. Krause and R. Herbst and M. Hänel and
M. Hanoun and U. Kaiser and M. Kaufmann and Z. Rácil and J.
Mayer and U. Oelschlägel and W. E. Berdel and G. Ehninger
and H. Serve and C. Müller-Tidow$^*$ and U. Platzbecker and
C. D. Baldus and A. Dahl and J. Schetelig and M.
Bornhäuser$^*$ and J. M. Middeke and C. Thiede},
title = {{M}utated {IKZF}1 is an independent marker of adverse risk
in acute myeloid leukemia.},
journal = {Leukemia},
volume = {37},
number = {12},
issn = {0887-6924},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2023-02070},
pages = {2395-2403},
year = {2023},
note = {2023 Dec;37(12):2395-2403},
abstract = {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.},
cin = {A360 / A350 / DD01},
ddc = {610},
cid = {I:(DE-He78)A360-20160331 / I:(DE-He78)A350-20160331 /
I:(DE-He78)DD01-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37833543},
doi = {10.1038/s41375-023-02061-1},
url = {https://inrepo02.dkfz.de/record/284759},
}