{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:00:23Z","timestamp":1792414823342,"version":"4.4.0"},"reference-count":52,"publisher":"American Society of Hematology","issue":"15","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,9]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The contribution of clonal hematopoiesis (CH) and disease-initiating precursors in B-cell non-Hodgkin lymphomas (B-NHLs) remains underexplored. Such precursors may drive clonal evolution, contributing to disease progression and relapse. Here, we systematically profiled genetic precursor lesions in 43 patients with B-NHL using complementary whole-exome, targeted, and single-cell sequencing approaches. CH-associated mutations with a variant allele frequency of \u22651% were detected in the peripheral blood of 55% of patients, with significantly higher frequencies in indolent compared with aggressive B-NHL (P = .03). Quantification of allele burden in flow-sorted cell populations revealed a B-cell\u2013skewed expansion of CH clones, contrasting the myeloid differentiation bias reported in individuals without hematologic malignancies. Gene-specific expansion patterns were evident among the most frequent CH lesions, with DNMT3A-mutant clones exhibiting impaired hematopoietic differentiation and TET2-mutant clones having multilineage 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 preneoplastic 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025030489","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T19:42:32Z","timestamp":1767642152000},"page":"1723-1734","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Clonal hematopoiesis and lymphoma-associated mutations in hematopoietic progenitors in B-cell non-Hodgkin lymphoma"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9917-7396","authenticated-orcid":false,"given":"Laura","family":"Wiegand","sequence":"first","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8476-9187","authenticated-orcid":false,"given":"Patricia","family":"Silva","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Noerenberg","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8868-2533","authenticated-orcid":false,"given":"Friederike","family":"Christen","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8912-6115","authenticated-orcid":false,"given":"Klara","family":"Kopp","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8482-4984","authenticated-orcid":false,"given":"Benjamin Nick","family":"Locher","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6222-5323","authenticated-orcid":false,"given":"Pelle","family":"L\u00f6we","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3196-6214","authenticated-orcid":false,"given":"Marlon","family":"Tilgner","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Altwasser","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Storzer","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9015-7671","authenticated-orcid":false,"given":"Catarina Marlene","family":"Stein","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5969-9467","authenticated-orcid":false,"given":"Franziska","family":"Briest","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4417-4750","authenticated-orcid":false,"given":"Christopher Maximilian","family":"Arends","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, 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and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"},{"name":"4German Cancer Consortium, Partner Site, Berlin, Germany"},{"name":"5Cluster of Excellence ImmunoPreCept, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9902-5424","authenticated-orcid":false,"given":"Il-Kang","family":"Na","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology, and Cancer Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin Institute of Health, Berlin, Germany"},{"name":"3Center of Digital Health, Berlin Institute of Health at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin, 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