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. 2025 Jul;39(7):1773-1777.
doi: 10.1038/s41375-025-02622-6. Epub 2025 Apr 28.

Prognostic impact of clonal representation of myelodysplasia-related gene mutations in acute myeloid leukemia

Rabea Mecklenbrauck  1   2 , Nora Borchert  1 , Razif Gabdoulline  1 , Piroska Poll  1 , Carolin Funke  1 , Maximilian Brandes  1 , Louisa-Kristin Dallmann  1 , Walter Fiedler  3 , Jürgen Krauter  4 , Arne Trummer  5 , Bernd Hertenstein  6 , Martin Müller  7 , Michael Lübbert  8 , Monika Schwalenberg  9 , Andreas Voss  10 , Nataliya Di Donato  11 , Anke Bergmann  11 , Verena Gaidzik  12 , Konstanze Döhner  12 , Hartmut Döhner  12 , Arnold Ganser  1 , Florian H Heidel  1   13 , Felicitas R Thol  1 , Michael Heuser  14   15
Affiliations

Prognostic impact of clonal representation of myelodysplasia-related gene mutations in acute myeloid leukemia

Rabea Mecklenbrauck et al. Leukemia. 2025 Jul.
No abstract available

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Conflict of interest statement

Competing interests: AV declares honoraria from BMS/Celgene, Delbert, Novartis, Pfizer, SOBI and travel support from Amgen. AT declares paid consultancy from BMS and Janssen. WF declares personal fees and non-financial support from AbbVie; grants, personal fees, and non-financial support from Amgen and Pfizer; and personal fees from Jazz Pharmaceuticals, Celgene, MorphoSys, Ariad/Incyte, Stemline Therapeutics, Clinigen, Daiichi Sankyo, Otsuka and Servier outside the submitted work; in addition, research support from Apis; patent issued with Amgen and support for medical writing for Amgen, Pfizer, and AbbVie. KD declares consultancy with honoraria from AbbVie, Janssen, Jazz, Novartis, Bristol Myers Squibb, Celgene; clinical research funding to institution from Novartis, AbbVie, Astellas, Bristol Myers Squibb, Celgene, Jazz Pharmaceuticals, Kronos Bio, Servier. HD declares honoraria from AbbVie, AstraZeneca, Gilead, Janssen, Jazz, Pfizer, Servier, Stemline, Syndax; clinical research funding to institution from AbbVie, Astellas, Bristol Myers Squibb, Celgene, Jazz Pharmaceuticals, Kronos Bio, Servier; Travel, accommodations, expenses from Abbvie, Servier. FHH served as an advisor for Novartis, CTI, Celgene/BMS, Janssen, Abbvie, GSK, Merck and AOP and received research funding from Novartis, Celgene/BMS and CTI. MH declares honoraria from Abbvie, Eurocept, Jazz Pharmaceuticals, Janssen, Novartis, Takeda, paid consultancy for Abbvie, Agios, BMS, Daiichi Sankyo, Glycostem, Jazz Pharmaceuticals, Kura Oncology, Novartis, Pfizer, PinotBio, Roche, Tolremo, and research funding to his institution from Abbvie, Agios, Astellas, Bayer Pharma AG, BergenBio, Daiichi Sankyo, Glycostem, Jazz Pharmaceuticals, Loxo Oncology, Novartis, Pfizer, PinotBio, Roche. Ethics approval and consent to participate: Written informed consent was obtained according to the Declaration of Helsinki and the study was approved by the local ethics review committee of Hannover Medical School (ethical vote 936-2011 and 1187-2011). Since 2012 all patients were included in the AMLSG-BiO registry. All described methods were performed in accordance with the relevant guidelines and regulations.

Figures

Fig. 1
Fig. 1. Prognostic impact of the size of the MRG mutated clone.
A Among the 156 patients bearing at least one MRG mutation and classified as ELN adverse risk, the highest VAF was chosen to calculate a prognostically relevant VAF cut-off using maximally selected rank statistics. The most discriminating cut-off was 45%. B Event-free and C overall survival of patients with at least one MRG mutation with a VAF ≥ 45% compared to patients where all MRG mutations have a VAF < 45%.
Fig. 2
Fig. 2. Impact of type of consolidation therapy on the outcome of patients with MRG mutations.
A Simon-Makuch plot showing the time-adjusted overall survival of all low VAF patients considering allogeneic stem cell transplantation as a time dependent-variable. 3 patients had to be excluded from the analysis due to missing data. B Same as in A but for high VAF patients. 2 patients had to be excluded from the analysis due to missing data. C Competing risk analysis of MRG low vs. high VAF patients receiving alloHCT in first CR/CRi. CIR cumulative incidence of relapse, NRM non-relapse mortality. 3 patients had to be excluded from the analysis due to missing data.
See this image and copyright information in PMC

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