Authors: Nicolas Duployez, Loïc Vasseur, Rathana Kim, Laëtitia Largeaud, Marie Passet, Anaïs L’Haridon, Pierre Lemaire, Laurène Fenwarth, Sandrine Geffroy, Nathalie Helevaut, Karine Celli‑Lebras, Lionel Adès, Delphine Lebon, Céline Berthon, Alice Marceau-Renaut, Meyling Cheok, Juliette Lambert, Christian Récher, Emmanuel Raffoux, Jean-Baptiste Micol, Arnaud Pigneux, Claude Gardin, Eric Delabesse, Jean Soulier, Mathilde Hunault, Hervé Dombret, Raphael Itzykson, Emmanuelle Clappier, Claude Preudhomme
Published: 2023-04-21
DOI: 10.1038/s41375-023-01906-z
Source: Full article
AbstractTandem duplications (TDs) of theUBTFgene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found thatUBTF-TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults withUBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates ofWT1mutations (61%),FLT3-ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence ofFLT3-ITD.UBTF-TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) thanUBTF-wild-type patients. In patients enrolled in the ALFA-0702 study (n = 614 patients including 21 withUBTF-TD AML), the 3-year disease-free survival (DFS) and overall survival ofUBTF-TD patients were 42.9% (95%CI: 23.4–78.5%) and 57.1% (95%CI: 39.5–82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests thatWT1-mutated clones are frequently selected under ICT. This study supports the recognition ofUBTF-TD AML as a new AML entity in adults.