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December 8, 2025BloodOpen Access

Tracing the evolution of clonal T cell responses in LGL leukemia with single-cell whole genome sequencing

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Authors

AHAino HäkkinenUniversity of HelsinkiSLSofie LundgrenUniversity of HelsinkiRBRuben van BoxtelOncode Institute

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Implication

Single-cell whole genome sequencing reveals distinct clonal evolution and somatic mutations in T cells of T-LGLL patients, indicating complex disease mechanisms.

Key Points

  • This research aims to understand the clonal evolution and genetic mutations of T cells in T-LGLL using single-cell sequencing techniques.
  • Utilized single-cell whole genome sequencing (scWGS) of T cells from 5 T-LGLL patients
  • Genotyped DNA to identify STAT3 mutations in sorted T cells
  • Analyzed mutation burden and phylogenetic trees based on T cell lineages
  • Identified a higher somatic mutation burden in STAT3 mutated T cells compared to wild-type counterparts in some patients
  • Phylogenetic analysis indicated unique clonal structures for each patient
  • Highlighted the timing of STAT3 variant acquisition relative to TCR rearrangement, suggesting complex evolution patterns.

Cite This Study

Häkkinen et al. (2025) studied this question.

synapsesocial.com/papers/69362f7f4fa91c937236e563https://doi.org/10.1182/blood-2025-3523
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Also Consider

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

  1. 1T-cell large granular lymphocyte leukaemia with pure red cell aplasia harbouring a somatic STAT3 P715L mutation2026
  2. 2Indolent γδ CD4−/CD8− double negative T-large granular lymphocytic leukemia with a STAT5B T628S mutation: a case report2026
  3. 3Functional analysis of STAT3 activating mutations in LGL leukemia reveals epigenetic reprograming and therapeutic vulnerabilities.2025
  4. 4Analysis of CD8 cytotoxic t-cells in patients with myelodysplastic syndrome (MDS) and T-cell large granulocyte lymphocytic leukemia (T-LGLL) reveal a distinct phenotype compared to those with t-lgll2025
  5. 5High prevalence and immunophenotypic diversity of clonal T‑large granular lymphocytes in JAK2‑mutated myeloproliferative neoplasms2026