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| Item Type: | Article |
|---|---|
| Title: | Clonal hematopoiesis and lymphoma-associated mutations in hematopoietic progenitors in B-cell non-Hodgkin lymphoma |
| Creators Name: | Wiegand, Laura, Silva, Patricia, Noerenberg, Daniel, Christen, Friederike, Kopp, Klara, Locher, Benjamin Nick, Löwe, Pelle, Tilgner, Marlon, Altwasser, Robert, Storzer, Vanessa, Stein, Catarina Marlene, Briest, Franziska, Arends, Christopher Maximilian, Frick, Mareike, Ihlow, Jana, Dolnik, Anna, Ishaque, Naveed, Keller, Ulrich, Na, Il-Kang, Penter, Livius, Bullinger, Lars, Hablesreiter, Raphael and Damm, Frederik |
| Abstract: | Gene-specific expansion patterns were evident among the most frequent CH lesions, with DNMT3A-mutant clones exhibiting impaired hematopoietic differentiation and TET2-mutant clones showing multi-lineage propagation. Notably, identical CH clones were detected in 41% of corresponding lymphomas, displaying distinct clonal dynamics: tumor-promoting CH (expansion in B-NHL; 10/16 clones; mainly TP53) and tumor-infiltrating CH (no expansion; mainly DNMT3A). Moreover, we identified lymphoma-associated mutations in flow-sorted hematopoietic progenitors from patients with indolent but not aggressive B-NHL and observed a stepwise accumulation of mutations along the lymphoid differentiation path. Single-cell genotyping confirmed the presence of mutated progenitors in 3 follicular, 2 mantle cell and 2 marginal zone lymphoma patients, providing direct evidence of a pre-neoplastic state in disease pathogenesis. Our findings offer novel insight into the cellular origin of nodal B-NHLs and highlight a previously underappreciated role for early clonal events involving the stem/progenitor cell compartment. |
| Source: | Blood |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date: | 7 January 2026 |
| Official Publication: | https://doi.org/10.1182/blood.2025030489 |
| PubMed: | View item in PubMed |
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