Evidence map›Paper›PMID 41566085›Full record

ArticleAnnals of hematology2026

PRDM16 expression is an independent prognostic factor in AML with the double-mutant NPM1/FLT3-ITD genotype.

Sebastian Stasik, Jan-Niklas Eckardt, Christoph Röllig, Claudia D Baldus, Hubert Serve, Carsten Müller-Tidow, Kerstin Schäfer-Eckart, Martin Kaufmann, Stefan W Krause, Mathias Hänel and 7 more

Abstract read
In one paragraph

Article in Annals of hematology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Sebastian StasikMedizinische Klinik und Poliklinik I, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Jan-Niklas EckardtMedizinische Klinik und Poliklinik I, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Christoph RölligMedizinische Klinik und Poliklinik I, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Claudia D BaldusKlinik Für Innere Medizin II, Universitätsklinikum Schleswig-Holstein, Hämatologie Und Onkologie, Kiel, Germany.
Hubert ServeMedizinische Klinik II, Universitätsklinikum Frankfurt, Frankfurt Am Main, Germany.
Carsten Müller-TidowMedizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany.
Kerstin Schäfer-EckartKlinik Für Innere Medizin V, Klinikum Nürnberg Nord, Nuremberg, Germany.
Martin KaufmannAbteilung Für Hämatologie, Onkologie Und Palliativmedizin, Robert-Bosch-Krankenhaus, Stuttgart, Germany.
Stefan W KrauseMedizinische Klinik 5, Universitätsklinikum Erlangen, Erlangen, Germany.
Mathias HänelMedizinische Klinik III, Klinikum Chemnitz, Chemnitz, Germany.
Andreas NeubauerKlinik Für Hämatologie, Philipps Universität Marburg, Onkologie, ImmunologieMarburg, Germany.
Gerhard EhningerMedizinische Klinik und Poliklinik I, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Uwe PlatzbeckerMedizinische Klinik und Poliklinik I, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Martin BornhäuserMedizinische Klinik und Poliklinik I, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Johannes ScheteligMedizinische Klinik und Poliklinik I, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Jan M MiddekeMedizinische Klinik und Poliklinik I, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Christian ThiedeMedizinische Klinik und Poliklinik I, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. christian.thiede@uniklinikum-dresden.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

PRDM16 (PR Domain Containing 16) is a transcription factor that plays a critical role in hematopoietic stem cell maintenance. In acute myeloid leukemia (AML), PRDM16 overexpression is linked to specific cytogenetic risk groups and poor prognosis. However, in NPM1-mutated AMLs, PRDM16 expression varies widely, with no consensus on its prognostic significance. To understand molecular and clinical associations of PRDM16 expression in this relevant subgroup, we screened 503 adult NPM1-mutant AML patients. High PRDM16 expression was associated with mutations in DNMT3A (57% vs 22%; p < 0.0001) and FLT3-ITD (51% vs 37%; p = 0.0258), and therefore a higher rate of ELN2022 intermediate-risk (42% vs 26%; p = 0.01), compared to low PRDM16 expression. Accordingly, PRDM16 overexpression was not associated with clinical outcome in multivariable analysis adjusting for ELN2022 risk in the unselected NPM1-mutant AML cohort. However, within the double-mutant NPM1/FLT3-ITD subgroup (n = 200), low PRDM16 expression was an independent prognostic factor for longer survival (hazard ratio [95%-CI] 0.467 [0.270-0.807]; p = 0.006). On a molecular level, low PRDM16 expression was associated with mutations in epigenetic regulators (TET2, IDH1/2) and increased PRDM16 promoter methylation, suggesting impaired TET/IDH-mediated DNA-demethylation as underlying mechanism. Notably, IDH1 R132C and IDH2 R140Q alterations particularly contributed to higher PRDM16 promoter methylation and reduced expression. These results suggest an association of PRDM16 overexpression with the NPM1/FLT3-ITD/DNMT3A triple-mutant AML genotype, typically linked to high leukemia stem cell frequencies and poor prognosis. Importantly, within this adverse AML subtype low PRDM16 expression is an independent prognostic marker for favorable outcome, supporting an anti-leukemic mechanism in AMLs with repressed PRDM16 transcription.

Indexed as

DNA-Binding Proteinsfms-Like Tyrosine Kinase 3Gene Expression Regulation, LeukemicLeukemia, Myeloid, AcuteMutationNuclear ProteinsTranscription FactorsAdultAgedDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AFemaleGenotypeHumansMaleMiddle AgedDNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanFLT3 protein, humanfms-Like Tyrosine Kinase 3NPM1 protein, humanNuclear ProteinsNucleophosminPRDM16 protein, humanTranscription FactorsAcute Myeloid Leukemia (AML)Clinical OutcomeMolecular associationsPRDM16 expression

Identifiers

PMID41566085
PMCPMC12823675

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.