biostudies-literatureUnknown10(2)Cosentino CThe 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-seq using a 28-gene 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-related <i>TP53</i> mutations, were restricted to the myelomonocytic compartment and absent in CLL cells, as also documented by single-cell DNA sequencing. CH associated with shorter overall survival (OS) (hazard ratio [HR] 1.36, 95% CI 1.04-1.77, P = 0.023); specifically, <i>TET2</i> mutations independently predicted inferior OS (HR 1.62, 95% CI 1.15-2.28, P = 0.01) after adHemaSpheree70322https://www.ebi.ac.uk/biostudies/studies/S-EPMC12907972biostudies-literatureDissecting clonal hematopoiesis in the myeloid compartment of chronic lymphocytic leukemia and Richter transformation.PMC12907972Lazzaro MGhanej JFumagalli LPerutelli FTerzi di Bergamo LRossi DFoa RCoscia MTrentin LCardinali DCividini LKogila SMahmoud AMDeambrogi CMaiellaro FCosentino CIannelli FScarfo LVitale CGhia PSalehi MMaher NPileri SGattei VRasi SZucchetto ARomano ISecomandi ECappelli LVNawabi MRAlmasri MAl Deeban BGaglio AChiarle RCaneparo VVisentin ANabki JGriggio VMouhssine SBellia MDel Giudice INicolosi MAlbi EDondolin RGaidano GMoia RfalseDissecting clonal hematopoiesis in the myeloid compartment of chronic lymphocytic leukemia and Richter transformation.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-seq using a 28-gene 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-related <i>TP53</i> mutations, were restricted to the myelomonocytic compartment and absent in CLL cells, as also documented by single-cell DNA sequencing. CH associated with shorter overall survival (OS) (hazard ratio [HR] 1.36, 95% CI 1.04-1.77, P = 0.023); specifically, <i>TET2</i> mutations independently predicted inferior OS (HR 1.62, 95% CI 1.15-2.28, P = 0.01) after ad2026-01-01T00:00:00Z2026 Feb2026-07-16T05:10:39.384Z2026-07-09T10:36:38.36ZS-EPMC129079724170454910.1002/hem3.70322