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

Nicolas Duployez (1, 2) , Loïc Vasseur (3) , Rathana Kim , Laëtitia Largeaud (4, 5, 6) , Marie Passet (7) , Anaïs L’haridon , Pierre Lemaire , Laurène Fenwarth (8) , Sandrine Geffroy (8, 9) , Nathalie Helevaut (8, 9) , Lionel Adès (10, 11) , Delphine Lebon (12, 13) , Céline Berthon (9) , Alice Marceau-Renaut (8) , Meyling Cheok (14, 8) , Juliette Lambert (15) , Christian Récher (16) , Emmanuel Raffoux (17) , Jean-Baptiste Micol (18) , Arnaud Pigneux (19) , Claude Gardin , Eric Delabesse , Jean Soulier , Mathilde Hunault , Hervé Dombret , Raphael Itzykson , Emmanuelle Clappier , Claude Preudhomme

1 Service de pathologie [CHU Lille]
2 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
3 GenCellDi (U944 / UMR7212) - Génomes, biologie cellulaire et thérapeutiques
4 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
5 UT3 - Université Toulouse III - Paul Sabatier
6 CRCT - Centre de Recherches en Cancérologie de Toulouse
7 Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière]
8 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
9 CHU Lille
10 AP-HP - Hopital Saint-Louis [AP-HP]
11 UPCité - Université Paris Cité
12 CHU Amiens-Picardie
13 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
14 IRCL - Institut pour la recherche sur le cancer de Lille [Lille]
15 UMR E007 - Thérapie génique et contrôle de l'expansion cellulaire
16 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
17 Service d'hématologie adulte [Hôpital de Saint Louis]
18 Département d'hématologie [Gustave Roussy]
19 Hôpital Haut-Lévêque

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.

Domaines: Médecine humaine et pathologie

Nicolas Duployez, Loïc Vasseur, Rathana Kim, Laëtitia Largeaud, Marie Passet, et al.. UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia. Leukemia, 2023, ⟨10.1038/s41375-023-01906-z⟩. ⟨hal-04083776⟩