biostudies-literatureUnknown104(7)Tran Quang VThe present longitudinal study reports a unique patient followed over almost three decades who sequentially developed polycythemia vera, chronic myelomonocytic leukemia, and chronic myeloid leukemia. The patient received successive hydroxyurea, ruxolitinib, and a combination of ruxolitinib and nilotinib. The clonal architecture dynamic was reconstructed using targeted high throughput asymmetric capture sequencing, allowing detection and quantification of mutations in 43 myeloid genes and BCR::ABL1 fusion in multiple bone marrow or peripheral blood samples and in single cell-derived colonies obtained from bone marrow colony-forming cell assays. This analysis has uncovered an unexpected subclonal link between three myeloid malignancies, all stemming from a DNMT3A/TET2 double mutant clone. OvAnnals of hematology3881-3887https://www.ebi.ac.uk/biostudies/studies/S-EPMC12334534biostudies-literatureSubclonal emergence of polycythemia vera, chronic myelomonocytic leukemia, and chronic myeloid leukemia.PMC12334534Etancelin PWagner-Ballon OSloma IBarathon QCretin JJoy CPautas CLoyaux RBen Jedidia BGricourt GTran Quang VTarfi SRoy LfalseSubclonal emergence of polycythemia vera, chronic myelomonocytic leukemia, and chronic myeloid leukemia.The present longitudinal study reports a unique patient followed over almost three decades who sequentially developed polycythemia vera, chronic myelomonocytic leukemia, and chronic myeloid leukemia. The patient received successive hydroxyurea, ruxolitinib, and a combination of ruxolitinib and nilotinib. The clonal architecture dynamic was reconstructed using targeted high throughput asymmetric capture sequencing, allowing detection and quantification of mutations in 43 myeloid genes and BCR::ABL1 fusion in multiple bone marrow or peripheral blood samples and in single cell-derived colonies obtained from bone marrow colony-forming cell assays. This analysis has uncovered an unexpected subclonal link between three myeloid malignancies, all stemming from a DNMT3A/TET2 double mutant clone. Ov2025-01-01T00:00:00Z2025 Jul2026-04-15T19:07:45.913Z2026-04-07T14:00:51.862ZS-EPMC123345344041159710.1007/s00277-025-06417-8