{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T20:50:24Z","timestamp":1789159824897,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The clinical and biological significance of clonal hematopoiesis (CH) has not been investigated in the myeloid compartment of chronic lymphocytic leukemia (CLL). By studying 488 newly diagnosed CLL through CAPP\u2010seq using a 28\u2010gene panel on granulocyte genomic DNA (gDNA), CH occurred in 231 (47.3%) patients. Cell sorting of cases that never developed Richter transformation (RT) confirmed that CH mutations, including CH\u2010related\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations, were restricted to the myelomonocytic compartment and absent in CLL cells, as also documented by single\u2010cell DNA sequencing. CH associated with shorter overall survival (OS) (hazard ratio [HR] 1.36, 95% CI 1.04\u20131.77, P\u2009=\u20090.023); specifically,\n                    <jats:italic>TET2<\/jats:italic>\n                    mutations independently predicted inferior OS (HR 1.62, 95% CI 1.15\u20132.28, P\u2009=\u20090.01) after adjusting for age and for CLL\u2010related prognostic biomarkers, namely IGHV and\n                    <jats:italic>TP53<\/jats:italic>\n                    status. Regarding therapy\u2010related toxicities, CH correlated with a higher incidence of Grade \u2265 3 neutropenia (P\u2009=\u20090.004) after venetoclax\u2010based regimens. Sequential samples (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200957) analysis showed that Bruton tyrosine kinase (BTK) and BCL2 inhibitors do not induce CH expansion, which was instead driven by chemotherapy. CH is significantly associated with a higher risk of second hematological malignancies only in chemo\u2010exposed patients. Single\u2010cell RNA sequencing of seven CH+ and six CH\u2212 CLL revealed that the T\u2010cell compartment of CH+ patients exhibits a less exhausted phenotype, documented by lower expression of TOX, the master regulator of T\u2010cell exhaustion, and a higher pro\u2010inflammatory profile. CH also influenced RT, since CH\n                    <jats:italic>ASXL1<\/jats:italic>\n                    mutations independently associated with higher RT risk (HR 11.19, 95% CI 4.09\u201330.62, P\u2009&lt;\u20090.001). Overall, CH in CLL impacts survival, therapeutic toxicity, and transformation risk while also influencing the T\u2010cell immune compartment.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70322","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:00:58Z","timestamp":1771239658000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dissecting clonal hematopoiesis in the myeloid compartment of chronic lymphocytic leukemia and Richter transformation"],"prefix":"10.1002","volume":"10","author":[{"given":"Chiara","family":"Cosentino","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine Universit\u00e0 del Piemonte Orientale and AOU Maggiore della Carit\u00e0 di Novara Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Mouhssine","sequence":"additional","affiliation":[{"name":"Division 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