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December 8, 2025BloodOpen Access

Phenotypic heterogeneity and remodeling drive resistance to venetoclax treatment in acute myeloid leukemia

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Authors

KFKen FurudateZLZongrui LiMLMinggao Liang

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Overview

Integrative analysis reveals that phenotypic heterogeneity drives resistance to venetoclax in acute myeloid leukemia patients, highlighting distinct cellular changes and mutations.

Key Points

  • This research investigates the cellular mechanisms driving resistance to venetoclax in acute myeloid leukemia.
  • Analyzed samples from a clinical trial using bulk RNA sequencing and single-cell RNA sequencing.
  • Developed a 25-gene VEN-resistance score using LASSO logistic regression to predict treatment response.
  • Performed computational deconvolution of RNA-seq data using CIBERSORTx to study cell composition.
  • Conducted DNA-antibody sequencing on longitudinal samples to assess genetic changes driving phenotypic remodeling.
  • Identified enriched non-responder clusters with higher KRAS mutation frequencies and different cell compositions.
  • Developed a VEN-resistance score that distinguished treatment responses with high statistical significance.
  • Noted significant phenotypic changes correlating with resistance, including decreases in stem cells and increases in erythroid cells.

Cite This Study

Furudate et al. (2025) studied this question.

synapsesocial.com/papers/69362f5d4fa91c937236dc57https://doi.org/10.1182/blood-2025-222
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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. 2Abstract 3400: Single-cell proteogenomics analysis of AML samples treated with decitabine and venetoclax reveals divergent treatment escape mechanisms2024
  3. 3Single-cell insights into acute myeloid leukemia treated with venetoclax-based therapy2025
  4. 4Abstract 5852: Tumor gene expression patterns affecting response to BCl-2 inhibitor venetoclax in acute myeloid leukemia2024
  5. 5Drivers of clinical resistance to venetoclax and hypomethylating agents in acute myeloid leukemia and strategies for improving efficacy2026 · 2 citations