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

001     308899
005     20260128120606.0
024 7 _ |a 10.1007/s00277-026-06767-x
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024 7 _ |a 0006-5242
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024 7 _ |a 1432-0584
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037 _ _ |a DKFZ-2026-00216
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Stasik, Sebastian
|b 0
245 _ _ |a PRDM16 expression is an independent prognostic factor in AML with the double-mutant NPM1/FLT3-ITD genotype.
260 _ _ |a New York
|c 2026
|b Springer
336 7 _ |a article
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520 _ _ |a 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.
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
650 _ 7 |a PRDM16 expression
|2 Other
650 _ 7 |a Acute Myeloid Leukemia (AML)
|2 Other
650 _ 7 |a Clinical Outcome
|2 Other
650 _ 7 |a Molecular associations
|2 Other
650 _ 7 |a Nucleophosmin
|0 117896-08-9
|2 NLM Chemicals
650 _ 7 |a NPM1 protein, human
|2 NLM Chemicals
650 _ 7 |a fms-Like Tyrosine Kinase 3
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a FLT3 protein, human
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a Nuclear Proteins
|2 NLM Chemicals
650 _ 7 |a DNA-Binding Proteins
|2 NLM Chemicals
650 _ 7 |a Transcription Factors
|2 NLM Chemicals
650 _ 7 |a PRDM16 protein, human
|2 NLM Chemicals
650 _ 7 |a DNA Methyltransferase 3A
|0 EC 2.1.1.37
|2 NLM Chemicals
650 _ 7 |a DNMT3A protein, human
|2 NLM Chemicals
650 _ 7 |a DNA (Cytosine-5-)-Methyltransferases
|0 EC 2.1.1.37
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Nucleophosmin
|2 MeSH
650 _ 2 |a Leukemia, Myeloid, Acute: genetics
|2 MeSH
650 _ 2 |a Leukemia, Myeloid, Acute: mortality
|2 MeSH
650 _ 2 |a Leukemia, Myeloid, Acute: diagnosis
|2 MeSH
650 _ 2 |a Leukemia, Myeloid, Acute: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a fms-Like Tyrosine Kinase 3: genetics
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Nuclear Proteins: genetics
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: genetics
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: biosynthesis
|2 MeSH
650 _ 2 |a Transcription Factors: genetics
|2 MeSH
650 _ 2 |a Transcription Factors: biosynthesis
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Prognosis
|2 MeSH
650 _ 2 |a Mutation
|2 MeSH
650 _ 2 |a DNA Methyltransferase 3A
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Leukemic
|2 MeSH
650 _ 2 |a Genotype
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Young Adult
|2 MeSH
650 _ 2 |a DNA (Cytosine-5-)-Methyltransferases: genetics
|2 MeSH
700 1 _ |a Eckardt, Jan-Niklas
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700 1 _ |a Röllig, Christoph
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700 1 _ |a Baldus, Claudia D
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700 1 _ |a Serve, Hubert
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700 1 _ |a Müller-Tidow, Carsten
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700 1 _ |a Schäfer-Eckart, Kerstin
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700 1 _ |a Kaufmann, Martin
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700 1 _ |a Krause, Stefan W
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700 1 _ |a Hänel, Mathias
|b 9
700 1 _ |a Neubauer, Andreas
|b 10
700 1 _ |a Ehninger, Gerhard
|b 11
700 1 _ |a Platzbecker, Uwe
|b 12
700 1 _ |a Bornhäuser, Martin
|0 P:(DE-He78)2a9091646ed378ef030a77fd32aedf79
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700 1 _ |a Schetelig, Johannes
|b 14
700 1 _ |a Middeke, Jan M
|b 15
700 1 _ |a Thiede, Christian
|b 16
773 _ _ |a 10.1007/s00277-026-06767-x
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