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December 8, 2025BloodOpen Access

Mechanistic dissection of venetoclax sensitivity in AML through single-molecule BCL2 protein complex profiling and mutation-specific apoptotic rewiring

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Authors

LGLilly GuEKEun‐Young KimHLHong-Won Lee

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Overview

Analysis of protein–protein interactions reveals mutation-specific apoptotic profiles in acute myeloid leukemia, suggesting paths for personalized venetoclax treatment.

Key Points

  • Dynamic shifts in BCL2-family protein interactions during venetoclax therapy determine treatment outcome.
  • Elevated BCL2–BAX complexes were linked to persistent apoptotic resistance in non-responders to venetoclax plus hypomethylating agents.
  • Single-molecule protein interaction detection was employed to analyze complex dynamics across various mutation backgrounds in AML.
  • Findings highlight the need for a biomarker-driven strategy to personalize treatment for patients with acute myeloid leukemia.

Cite This Study

Gu et al. (2025) studied this question.

synapsesocial.com/papers/69362f514fa91c937236d95chttps://doi.org/10.1182/blood-2025-341
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Also Consider

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

  1. 1Single-cell transcriptomic insights into venetoclax response and resistance in secondary AML evolving from MDS2025
  2. 2IDH1 mutation predicts response and survival in treatment-naïve Acute Myeloid Leukemia patients receiving with venetoclax with a hypomethylating agent2025
  3. 3Venetoclax dosages, BH3 profiling, and bcl-2 expression predict response to azacitidine + venetoclax regimen in first line AML not eligible to intensive chemotherapy: First results of venetacible study2025
  4. 4Phenotypic heterogeneity and remodeling drive resistance to venetoclax treatment in acute myeloid leukemia2025 · 1 citations
  5. 5Factors affecting response and resistance to venetoclax in acute myeloid leukemia2025 · 6 citations