TY - JOUR
T1 - UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
AU - Duployez, Nicolas
AU - Vasseur, Loïc
AU - Kim, Rathana
AU - Largeaud, Laëtitia
AU - Passet, Marie
AU - L’Haridon, Anaïs
AU - Lemaire, Pierre
AU - Fenwarth, Laurène
AU - Geffroy, Sandrine
AU - Helevaut, Nathalie
AU - Celli‑Lebras, Karine
AU - Adès, Lionel
AU - Lebon, Delphine
AU - Berthon, Céline
AU - Marceau-Renaut, Alice
AU - Cheok, Meyling
AU - Lambert, Juliette
AU - Récher, Christian
AU - Raffoux, Emmanuel
AU - Micol, Jean Baptiste
AU - Pigneux, Arnaud
AU - Gardin, Claude
AU - Delabesse, Eric
AU - Soulier, Jean
AU - Hunault, Mathilde
AU - Dombret, Hervé
AU - Itzykson, Raphael
AU - Clappier, Emmanuelle
AU - Preudhomme, Claude
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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. [Figure not available: see fulltext.].
AB - 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. [Figure not available: see fulltext.].
UR - http://www.scopus.com/inward/record.url?scp=85153202931&partnerID=8YFLogxK
U2 - 10.1038/s41375-023-01906-z
DO - 10.1038/s41375-023-01906-z
M3 - Article
AN - SCOPUS:85153202931
SN - 0887-6924
VL - 37
SP - 1245
EP - 1253
JO - Leukemia
JF - Leukemia
IS - 6
ER -