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December 8, 2025BloodOpen Access

Phylogenetic reconstruction reveals early divergence and late expansion of focal lesions in multiple myeloma

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Authors

KMKylee MaclachlanMemorial Sloan Kettering Cancer CenterPRPhilipp ReichertHeidelberg UniversitySHStefanie HuhnHeidelberg University

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Overview

Phylogenetic reconstruction reveals clonal divergence and mutational signatures in multiple myeloma with implications for progression.

Key Points

  • This research aims to elucidate the timeline and mechanisms contributing to focal lesion formation in multiple myeloma.
  • Analyzed 27 newly diagnosed multiple myeloma patients with paired bone marrow and focal lesion samples.
  • Utilized multi-region whole-genome sequencing and mutational timing approaches for analysis.
  • Identified subclones using algorithms like MOBSTER and VIBER, and conducted single-cell RNA sequencing.
  • Phylogenetic trees showed a median of 3 subclones per patient, with distinct dominant subclones at various sites.
  • Focal lesion subclones had 390 additional mutations compared to major bone marrow subclones, indicating recent expansions.
  • A median lag of 14 years was observed before the emergence of focal lesions, revealing early spatial divergence.

Cite This Study

Maclachlan et al. (2025) studied this question.

synapsesocial.com/papers/69362f4b4fa91c937236d75dhttps://doi.org/10.1182/blood-2025-685
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Also Consider

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

  1. 1On the cellular origins of multiple myeloma2025
  2. 2Subclonal genomic heterogeneity shapes immune crosstalk and clinical outcomes in multiple myeloma2025
  3. 3Clonal timing of FLT3-ITD dictates evolutionary trajectory and phenotypic heterogeneity in acute myeloid leukemia2025
  4. 4Single-cell DNA sequencing uncovers synergistic co-mutations in multiple myeloma2025
  5. 5Dynamic Cytogenetic Evolution in Multiple Myeloma: Prognostic Implications from Diagnosis to First Relapse2026 · 1 citations