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

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

1 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
2 Institut de Pathologie [CHU Lille]
3 GenCellDis (U944 / UMR7212) - Génomes, biologie cellulaire et thérapeutiques
4 seqOIA - Laboratoire de Biologie Médicale SeqOIA [Paris]
5 AP-HP - Hopital Saint-Louis [AP-HP]
6 CRCT - Centre de Recherches en Cancérologie de Toulouse
7 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
8 UT3 - Université Toulouse III - Paul Sabatier
9 CHU Pitié-Salpêtrière [AP-HP]
10 Service d'Hémato-oncologie [CHU Saint-Louis]
11 CHU Amiens-Picardie
12 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
13 SMS - Service des Maladies du Sang [CHU Lille]
14 UMR E007 - Thérapie génique et contrôle de l'expansion cellulaire
15 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
16 Service d'hématologie adulte [Hôpital de Saint Louis]
17 Département d'hématologie [Gustave Roussy]
18 Hôpital Haut-Lévêque
19 ICAT - SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques

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, 37 (6), pp.1245-1253. ⟨10.1038/s41375-023-01906-z⟩. ⟨hal-04541085⟩