Journal Article

DKFZ-2024-01418

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.

Hernández-Sánchez, A. ; González, T. ; Sobas, M. ; Sträng, E. ; Castellani, G. ; Abáigar, M. ; Valk, P. J. M. ; Villaverde Ramiro, Á. ; Benner, A.DKFZ* ; Metzeler, K. H. ; Azibeiro, R. ; Tettero, J. M. ; Martínez-López, J. ; Pratcorona, M. ; Martínez Elicegui, J. ; Mills, K. I. ; Thiede, C. ; Sanz, G. ; Döhner, K. ; Heuser, M. ; Haferlach, T. ; Turki, A. T. ; Reinhardt, D. ; Schulze-Rath, R. ; Barbus, M. ; Hernández-Rivas, J. M. ; Huntly, B. ; Ossenkoppele, G. ; Döhner, H. ; Bullinger, L.

2024
Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41375-024-02333-4

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.

Note: 2024 Sep;38(9):1929-1937

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Contributing Institute(s):

1. C060 Biostatistik (C060)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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