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UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia

2023; Springer Nature; Volume: 37; Issue: 6 Linguagem: Inglês

10.1038/s41375-023-01906-z

1476-5551

Nicolas Duployez, Loïc Vasseur, Rathana Kim, Laëtitia Largeaud, Marie Passet, Anaïs L’Haridon, Pierre Lemaire, Laurène Fenwarth, Sandrine Geffroy, Nathalie Hélevaut, 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, Éric Delabesse, Jean Soulier, Mathilde Hunault, Hervé Dombret, Raphaël Itzykson, Emmanuelle Clappier, Claude Preudhomme,

Cancer Genomics and Diagnostics

Abstract Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF -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 with UBTF -TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3 -ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence of FLT3 -ITD. UBTF -TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) than UBTF -wild-type patients. In patients enrolled in the ALFA-0702 study ( n = 614 patients including 21 with UBTF -TD AML), the 3-year disease-free survival (DFS) and overall survival of UBTF -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 that WT1 -mutated clones are frequently selected under ICT. This study supports the recognition of UBTF -TD AML as a new AML entity in adults.