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Resolving leukemic stem cell heterogeneity and plasticity with single-cell multiomics.

Frank Y Huang1, Andreas Trumpp2, Patrick Stelmach2

  • 1Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM, gGmbH), Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.

Seminars in Hematology
|September 5, 2025
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Summary

Leukemic stem cells (LSCs) drive acute myeloid leukemia (AML) relapse and are highly diverse. Single-cell multiomics helps understand LSC heterogeneity for better AML diagnostics and treatments.

Keywords:
Acute myeloid leukemia (AML)Leukemic stem cells (LSCs)PlasticityTherapy response and resistanceVenetoclax

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Area of Science:

  • Hematology
  • Cancer Biology
  • Genomics

Background:

  • Acute myeloid leukemia (AML) is driven by diverse leukemic stem cells (LSCs).
  • LSC heterogeneity impacts therapy response and disease relapse.
  • Understanding LSC diversity is crucial for effective AML treatment.

Purpose of the Study:

  • To review the causes and consequences of LSC heterogeneity in AML.
  • To highlight advances in single-cell multiomics for dissecting LSC diversity.
  • To explore how these technologies can improve AML diagnostics and monitoring.

Main Methods:

  • Review of current scientific literature.
  • Focus on single-cell multiomics technologies (genomics, transcriptomics, epigenomics, proteomics).
  • Analysis of LSC heterogeneity and plasticity in AML.

Main Results:

  • LSC heterogeneity arises from genetic and non-genetic factors.
  • Single-cell multiomics provides high-resolution molecular snapshots of individual LSCs.
  • This technology enables a deeper understanding of LSC states and vulnerabilities.

Conclusions:

  • LSC heterogeneity presents challenges but also therapeutic opportunities in AML.
  • Single-cell multiomics is transforming the study of AML LSC diversity.
  • Advances in these technologies promise to revolutionize AML diagnostics and patient monitoring.