Journal Article

DKFZ-2026-00115

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Unravelling co-mutational patterns with prognostic implications in NPM1 mutated adult acute myeloid leukemia - a HARMONY study.

Hernández-Sánchez, A. ; Villaverde Ramiro, Á. ; Sträng, E. ; Turki, A. T. ; Abáigar, M. ; Versluis, J. ; Thomas, I. ; Sobas, M. ; Martínez Elicegui, J. ; Castellani, G. ; Benner, A.DKFZ* ; Azibeiro, R. ; Tettero, J. M. ; Mecklenbrauck, R. ; Martínez-López, J. ; Pratcorona, M. ; Mills, K. I. ; Sanz, G. ; Voso, M. T. ; Sören, L. ; Röllig, C. ; Thiede, C. ; Metzeler, K. H. ; Döhner, K. ; Heuser, M. ; Haferlach, T. ; Valk, P. J. ; Russell, N. ; Hernández-Rivas, J. M. ; Huntly, B. ; Ossenkoppele, G. ; Döhner, H. ; Bullinger, L.DKFZ*

2026
Springer Nature London

Abstract: NPM1-mutated (NPM1-mut) acute myeloid leukemia (AML) is generally associated with a more favorable outcome, although the presence of additional gene mutations can influence patient prognosis. We analyzed intensively-treated adult NPM1-mut AML patients included in the HARMONY Alliance database. A newly developed risk classification, which included combinations of co-mutations in FLT3-ITD, DNMT3A, IDH1/IDH2, and TET2 genes, was applied to a training cohort of NPM1-mut AML patients included in clinical trials (n = 1001), an internal validation cohort more representative of real-world settings (n = 762), and an external validation cohort enrolled in UK-NCRI trials (n = 585). The HARMONY classification considered 51.8% of the NPM1-mut AML training cohort patients as favorable, 24.8% as intermediate, and 23.4% as adverse risk, with median overall survival (OS) of 14.4, 2.2, and 0.9 years, respectively; p < 0.001), thereby reclassifying 42.7% of NPM1-mut patients into a different European LeukemiaNet (ELN) 2022 risk category. These results were confirmed both in an internal and external validation cohort. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making.

Note: #DKTKZFB26# / epub

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)
2. C060 Biostatistik (C060)

Research Program(s):

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

Appears in the scientific report 2026

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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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