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December 1, 2025Briefings in BioinformaticsOpen Access

Causal interaction inference of compensatory structures from single-cell perturb-seq in AML

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Authors

CCChangde ChengSASajesan AryalBCBrittany M. Curtiss

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Overview

Causal inference framework predicts resistance mechanisms in acute myeloid leukemia using epigenetic regulators, suggesting new drug combinations.

Key Points

  • Resistance was predicted by modeling the causal structure of the leukemia stem-cell epigenetic landscape, and validating predictions with pharmacologic inhibition.
  • The analysis identified synergistic pairs of epigenetic regulators that enhanced differentiation and cell death, as well as antagonistic pairs leading to resistance.
  • Using single-cell perturb-seq data from KMT2A-rearranged AML, the framework indicates that interaction inference may be simpler than previously assumed.
  • This mechanism-guided approach may enable rational prioritization of epigenetic drug combinations in acute myeloid leukemia and other cancers.

Cite This Study

Cheng et al. (2025) studied this question.

synapsesocial.com/papers/69402a8d2d562116f2902748https://doi.org/10.1093/bib/bbaf631.007
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Also Consider

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

  1. 1A perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged AML2025
  2. 2A Perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged acute myeloid leukemia2026 · 1 citations
  3. 3Epigenetic mechanisms of drug resistance in acute myeloid leukemia: advances in small-molecule targeted therapy2025 · 5 citations
  4. 4Methylome profiling reveals context-dependent chemo-resistance mechanisms and enhances risk stratification in AML2026
  5. 5An integrated multi-omics analysis reveals a core epigenetically-activated transcriptional network driving oncogenic signaling in acute myeloid leukemia2026