UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
23
02
2023
accepted:
17
04
2023
revised:
06
04
2023
medline:
8
6
2023
pubmed:
22
4
2023
entrez:
21
04
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37085611
doi: 10.1038/s41375-023-01906-z
pii: 10.1038/s41375-023-01906-z
pmc: PMC10244165
doi:
Substances chimiques
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
transcription factor UBF
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1245-1253Informations de copyright
© 2023. The Author(s).
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