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December 8, 2025Blood

Changing dogma regarding mutation primacy in acute myelogenous leukemia : Protein expression supersedes mutation status

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Authors

EMEunice MagalhãesBBBrandon BrownSCSamanta Catueno

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Overview

Analysis shows prognostic impact of protein expression in AML, suggesting targeted therapy may improve outcomes with Hypomethylating Agent and Venetoclax.

Key Points

  • To evaluate the impact of protein expression levels on prognosis in Acute Myelogenous Leukemia (AML) independent of mutation status.
  • Measured protein levels in 805 fresh, untreated AML samples using Reverse Phase Protein Arrays.
  • Normalized protein expression against normal bone marrow-derived CD34+ cells.
  • Calculated prognostic impact of 17 GFM-related proteins and their expression levels categorized as High or Low.
  • Used hierarchical clustering to identify proteomic signatures and their associations with overall survival.
  • 14 of 17 GFM-related proteins showed significant prognostic impact on overall survival.
  • High gain of function protein expression correlated with poor outcomes, while low levels of certain loss of function proteins were adverse.
  • Prognosis varied by therapy received; some proteins indicated better outcomes with specific treatments.
  • Identified 9 unique proteomic signatures associated with distinct survival outcomes.

Cite This Study

Magalhães et al. (2025) studied this question.

synapsesocial.com/papers/69362f574fa91c937236d9fdhttps://doi.org/10.1182/blood-2025-3492
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Also Consider

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

  1. 1Clinical implications of variant allele frequencies of genes in patients with acute myeloid leukemia2026
  2. 2Proteogenomic analysis of NPM1-mutated AML reveals clinical heterogeneity related to differentiation states and mitochondrial metabolism2025
  3. 3Determining sensitivity to FLT3 inhibitors prior to therapy in FLT3 mutant acute myelogenous leukemia2025
  4. 4Low protein expression of Janus kinase 2 (JAK2) is prognostically adverse and independent of mutation status in acute myelogenous leukemia2025
  5. 5Impact of Somatic Gene Mutations on Prognosis Prediction in De Novo AML: Unraveling Insights from a Systematic Review and Meta-Analysis2025 · 1 citations