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December 8, 2025Blood

Proteogenomic analysis of NPM1-mutated AML reveals clinical heterogeneity related to differentiation states and mitochondrial metabolism

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Authors

JJJosefine JakobGoethe University FrankfurtBHBjörn HäuplGoethe University FrankfurtFTFelicitas TholMedizinische Hochschule Hannover

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Overview

Proteogenomic analysis exposes mitochondrial metabolism variation in acute myeloid leukemia, suggesting poor prognosis linked to BCL2 expression.

Key Points

  • Immature NPM1-mutated AML exhibited a high Mito-score, predicting poorer patient outcomes with an event-free survival p-value of 0.026.
  • A comprehensive proteomic analysis quantified 7,223 proteins, correlating BCL2 expression with differentiation states in leukemia.
  • Assessment of gene signatures across 284 patients revealed distinct profiles, with immature AML enriched for FLT3-ITD and BCL2 expression.
  • This study emphasizes mitochondrial metabolism's relevance in disease heterogeneity and treatment response for AML with NPM1 mutations.

Cite This Study

Jakob et al. (2025) studied this question.

synapsesocial.com/papers/69362f3a4fa91c937236d421https://doi.org/10.1182/blood-2025-660
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Prognostic covariates associated with outcomes in patients with NPM1-mutated acute myeloid leukemia2025 · 3 citations
  2. 2A Comprehensive Genomic Analysis of Nucleophosmin (NPM1) in Acute Myeloid Leukemia2025 · 2 citations
  3. 3Prognostic Value of Molecular and Clinical Features in Patients with NPM1 Gene Mutation in Acute Myeloid Leukemia2025 · 1 citations
  4. 4Targeting CCL3+mono like LSC overcomes chemotherapy resistance in NPM1 mutant AML2025
  5. 5Spatial single-cell multiomics of the bone marrow microenvironment in NPM1-mutant Acute Myeloid Leukemia2025