Journal Article Case Reports Ppublish
PubMed: 40411597 DOI: 10.1007/s00277-025-06417-8
Subclonal emergence of polycythemia vera, chronic myelomonocytic leukemia, and chronic myeloid leukemia.
Ann Hematol 104(7):3881-3887
Authors: Violaine Tran Quang, Jules Cretin, Romain Loyaux, Bilel Ben Jedidia, Sihem Tarfi, Guillaume Gricourt, Quentin Barathon, Corine Joy, Pascaline Etancelin, Orianne Wagner-Ballon, Cécile Pautas, Lydia Roy, Ivan Sloma
Affiliations
- Univ Paris Est Créteil, INSERM, IMRB, Créteil, France. Département d'Hématologie et d'Immunologie biologiques, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France.
- Univ Paris Est Créteil, INSERM, IMRB, Créteil, France.
- Département d'Hématologie et d'Immunologie biologiques, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France.
- Centre de lutte contre le cancer Henri Becquerel, Laboratoire de génétique oncologique, Rouen, France.
- Service d'Hématologie, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France.
- Univ Paris Est Créteil, INSERM, IMRB, Créteil, France.
- Département d'Hématologie et d'Immunologie biologiques, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France.
Abstract
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. Over a period of more than 30 years, this clone underwent major telomere shortening. However, a striking sustained major molecular response of the terminal dominant clone carrying all driver mutations was achieved by combination therapy with nilotinib and ruxolitinib. The remaining clone driving both polycythemia and chronic myelomonocytic leukemia remained unaffected and evolved to myelofibrosis and proliferative CMML.
MeSH
Cells, Polycythemia Vera, Bone Marrow, Hematology, Leukemia, Myelomonocytic, Chronic, Leukemia, Leukemia, Myeloid, Polycythemia, Clone Cells, Leukemia, Myelogenous, Chronic, Bcr-Abl Positive, Mutation