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@ARTICLE{HernndezSnchez:291455,
author = {A. Hernández-Sánchez and T. González and M. Sobas and E.
Sträng and G. Castellani and M. Abáigar and P. J. M. Valk
and Á. Villaverde Ramiro and A. Benner$^*$ and K. H.
Metzeler and R. Azibeiro and J. M. Tettero and J.
Martínez-López and M. Pratcorona and J. Martínez Elicegui
and K. I. Mills and C. Thiede and G. Sanz and K. Döhner and
M. Heuser and T. Haferlach and A. T. Turki and D. Reinhardt
and R. Schulze-Rath and M. Barbus and J. M. Hernández-Rivas
and B. Huntly and G. Ossenkoppele and H. Döhner and L.
Bullinger},
title = {{R}earrangements involving 11q23.3/{KMT}2{A} in adult
{AML}: mutational landscape and prognostic implications - a
{HARMONY} study.},
journal = {Leukemia},
volume = {38},
number = {9},
issn = {0887-6924},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2024-01418},
pages = {1929-1937},
year = {2024},
note = {2024 Sep;38(9):1929-1937},
abstract = {Balanced rearrangements involving the KMT2A gene (KMT2Ar)
are recurrent genetic abnormalities in acute myeloid
leukemia (AML), but there is lack of consensus regarding the
prognostic impact of different fusion partners. Moreover,
prognostic implications of gene mutations co-occurring with
KMT2Ar are not established. From the HARMONY AML database
205 KMT2Ar adult patients were selected, 185 of whom had
mutational information by a panel-based next-generation
sequencing analysis. Overall survival (OS) was similar
across the different translocations, including
t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However,
independent prognostic factors for OS in intensively treated
patients were age >60 years (HR 2.1, p = 0.001), secondary
AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and
KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with
de novo AML < 60 years, KRAS and TP53 were the
prognostically most relevant mutated genes, as patients with
a mutation of any of those two genes had a lower complete
remission rate $(50\%$ vs $86\%,$ p < 0.001) and inferior OS
(median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic
stem cell transplantation in first complete remission was
able to improve OS (p = 0.003). Our study highlights the
importance of the mutational patterns in adult KMT2Ar AML
and provides new insights into more accurate prognostic
stratification of these patients.},
cin = {C060},
ddc = {610},
cid = {I:(DE-He78)C060-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38965370},
doi = {10.1038/s41375-024-02333-4},
url = {https://inrepo02.dkfz.de/record/291455},
}