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December 8, 2025Blood

Single-cell multiomics reveals molecular identities and clonal dynamics of MRD progression in Myelodysplastic Syndromes after stem cell transplant

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Authors

JLJae‐Hyun LeeWLWesley S. LuAVAlejandro Marinos Velarde

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Overview

Single-cell technology reveals MRD progression dynamics in myelodysplastic syndromes post stem cell transplant, suggesting novel targets for intervention.

Key Points

  • This research aims to uncover the molecular identities and clonal dynamics of measurable residual disease (MRD) in myelodysplastic syndromes (MDS) following stem cell transplant.
  • Developed a novel single-cell multi-omic workflow called CARAMEL-seq.
  • Analyzed 52 longitudinal bone marrow samples from 10 patients who relapsed and 3 who did not.
  • Profiled both malignant and immune compartments by sorting CD34⁺ and CD34⁻ bone marrow mononuclear cells.
  • Utilized clonal tracing methods integrating copy number variant data and mitochondrial variant probabilities.
  • CARAMEL-seq achieved near 10⁻⁷ sensitivity for MRD detection, identifying MRD cells in 9 of 10 relapsed patients.
  • Observed specific enrichment of MRD cells in the CD34⁺ compartment and identified novel markers of MRD.
  • Noted significant phenotypic and clonal evolution in post-SCT relapse, with dominant clones being selectively eliminated.
  • Found increased expression of TGF-β, hypoxia, and IFNγ pathways in relapsed MRD cells.

Cite This Study

Lee et al. (2025) studied this question.

synapsesocial.com/papers/69362f4e4fa91c937236d8c1https://doi.org/10.1182/blood-2025-674
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Also Consider

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

  1. 1MRD dynamics predicts progression and reveals a vulnerable state for immunotherapy interception in multiple myeloma2026
  2. 2Clinical translation of single cell measurable residual disease (scMRD) assay in real world Acute Myeloid Leukemia (AML) patients2025
  3. 3Measurable residual disease in newly diagnosed multiple myeloma: Experience from a large cohort from an academic medical center2025
  4. 4Relapse Despite <scp>MRD</scp> Negativity in Multiple Myeloma: Toward Integrated Risk Prediction2026 · 1 citations
  5. 5A novel multi-target NGS application for molecular monitoring of measurable residual disease in Acute Myeloid Leukemia2025 · 2 citations