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December 8, 2025Blood

Clonal architecture and dynamics of somatic evolution in aplastic anemia and paroxysmal nocturnal hemoglobinuria

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Authors

MCMichael Spencer ChapmanNWNick WilliamsEBE. Joanna Baxter

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Overview

Analysis uncovers somatic mutations and immune escape in aplastic anemia and PNH, suggesting new classifications.

Key Points

  • To investigate the clonal dynamics and evolutionary patterns in aplastic anemia and paroxysmal nocturnal hemoglobinuria.
  • Utilized whole-genome sequencing of single hematopoietic stem and progenitor cells
  • Cultured CD3-depleted peripheral blood HSPC-derived colonies in methylcellulose
  • Identified mutation timing and clonal trajectories from 10 patients with AA and PNH
  • Analyzed positive selection in somatic mutations using dN/dS method
  • Built high-resolution hematopoietic lineage trees to observe clonal architecture.
  • Distinct clonal landscapes observed in AA: myeloid driver predominant and immune escape predominant
  • Immune escape variants identified with recurrent mutations in ERAP1
  • Somatic mutations correlated with long-term outcomes; myeloid drivers expanded later while immune escapes emerged early
  • PIGA mutations observed prior to clinical onset of PNH, showing delayed clonal expansion pattern

Cite This Study

Chapman et al. (2025) studied this question.

synapsesocial.com/papers/69362f7f4fa91c937236e5f7https://doi.org/10.1182/blood-2025-25
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