UBTF tandem duplications in pediatric myelodysplastic syndrome and acute myeloid leukemia: implications for clinical screening and diagnosis.
Haematologica
; 109(8): 2459-2468, 2024 08 01.
Article
en En
| MEDLINE
| ID: mdl-38426285
ABSTRACT
Recent genomic studies in adult and pediatric acute myeloid leukemia (AML) demonstrated recurrent in-frame tandem duplications (TD) in exon 13 of upstream binding transcription factor (UBTF). These alterations, which account for approximately 4.3% of AML in childhood and about 3% in adult AML aged <60 years of age, are subtype-defining and associated with poor outcomes. Here, we provide a comprehensive investigation into the clinicopathological features of UBTF-TD myeloid neoplasms in childhood, including 89 unique pediatric AML and 6 myelodysplastic syndrome (MDS) cases harboring a tandem duplication in exon 13 of UBTF. We demonstrate that UBTF-TD myeloid tumors are associated with dysplastic features, low bone marrow blast infiltration, and low white blood cell count. Furthermore, using bulk and single-cell analyses, we confirm that UBTF-TD is an early and clonal event associated with a distinct transcriptional profile, whereas the acquisition of FLT3 or WT1 mutations is associated with more stem cell-like programs. Lastly, we report rare duplications within exon 9 of UBTF that phenocopy exon 13 duplications, expanding the spectrum of UBTF alterations in pediatric myeloid tumors. Collectively, we comprehensively characterize pediatric AML and MDS with UBTF-TD, and highlight key clinical and pathologic features that distinguish this new entity from other molecular subtypes of AML.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Síndromes Mielodisplásicos
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Leucemia Mieloide Aguda
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Duplicación de Gen
Límite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Haematologica
Año:
2024
Tipo del documento:
Article
País de afiliación:
Túnez