T-cell receptor architecture and clonal tiding provide insight into the transformation trajectory of peripheral T-cell lymphomas
| Autor: | Edith Willscher, Christoph Schultheiß, Lisa Paschold, Franziska Lea Schümann, Paul Schmidt-Barbo, Benjamin Thiele, Marcus Bauer, Claudia Wickenhauser, Thomas Weber, Mascha Binder |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Haematologica, Vol 999, Iss 1 (2024) |
| Druh dokumentu: | article |
| ISSN: | 0390-6078 1592-8721 |
| DOI: | 10.3324/haematol.2024.285395 |
| Popis: | While T cell lymphomas are classified as mature neoplasms, emerging evidence indicates that malignant transformation may occur at an earlier stage of T cell maturation. In this study, we determined clonal architectures in a broad range of T cell lymphomas. Our multidimensional profiling indicates that a large part of these lymphomas in fact emerge from an immature lymphoid T cell precursor at a maturation stage prior to V(D)J rearrangement that undergoes branching evolution. Consequently, at single cell resolution we observed considerable clonal tiding under selective therapeutic pressure. T cell receptor next-generation sequencing suggested a highly biased usage of TRBV20-1 gene segments as part of multiple antigen receptor rearrangements per patient. The predominance of TRBV20-1 was found across all major T cell lymphoma subtypes analyzed. This suggested that this particular V gene – independently of complementarity-determining region 3 (CDR3) configuration - may represent a driver of malignant transformation. Together, our data indicate that T cell lymphomas derive from immature lymphoid precursors and display considerable intratumoral heterogeneity that may provide the basis for relapse and resistance in these hard-to-treat cancers. |
| Databáze: | Directory of Open Access Journals |
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