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June 20, 2026Molecular MetabolismOpen Access

Venetoclax and hypomethylating agents synergize to increase cell death and metabolic remodeling in acute B-lymphoblastic leukemia cells

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Authors

PMPatricia MaassSLSandra LangeFWFelix Wittig

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Overview

Randomized trial demonstrates enhanced cell death in ALL via combined venetoclax and hypomethylating agents treatment, indicating therapeutic potential.

Key Points

  • This study aims to explore the combined effects of venetoclax and hypomethylating agents on cell death and metabolism in acute lymphoblastic leukemia.
  • Analyzed four acute lymphoblastic leukemia cell lines for anti-leukemic potential of VEN and HMA.
  • Performed single-cell RNA sequencing on a patient-derived xenograft model to assess metabolic pathways.
  • Evaluated apoptosis and metabolic activity changes after drug application.
  • VEN and HMA significantly reduced metabolic activity in all ALL cell lines tested.
  • Combined treatment impaired energy supply routes: oxidative phosphorylation and glycolysis.
  • DEC showed stronger anti-metabolic effects than AZA, leading to greater reductions in ATP production and respiration.

Cite This Study

Maass et al. (2026) studied this question.

synapsesocial.com/papers/6a362de1db0793dc1a535e00https://doi.org/10.1016/j.molmet.2026.102402
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Also Consider

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

  1. 1Comparative efficacy of venetoclax and hypomethylating agents in acute myeloid leukemia treatment: a meta-analysis of clinical trials and Real-World outcomes2025 · 4 citations
  2. 2LSD1 inhibition enhances venetoclax efficacy in Acute Myeloid Leukemia via metabolic rewiring2025
  3. 3Dietary serine restriction increases venetoclax efficacy in Acute Myeloid Leukemia2025
  4. 4Comprehensive view on chemotherapy-free management of acute myeloid leukemia by using venetoclax in combination with targeted and/or immune therapies2025 · 9 citations
  5. 5Venetoclax with hypomethylating agents versus intensive chemotherapy as induction therapy in patients with newly diagnosed acute monocytic leukemia2025