Faculty, Staff and Student Publications

Publication Date

4-1-2025

Journal

The American Journal of Surgical Pathology

DOI

10.1097/PAS.0000000000002350

PMID

39760616

PMCID

PMC11893000

PubMedCentral® Posted Date

1-6-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Tandem duplications (TDs) in exons of upstream binding transcription factor (UBTF-TD) are a rare recurrent alteration in pediatric and adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/neoplasm. Although recently identified, AML with UBTF-TD is now considered a distinct subtype of AML. To further our understanding of myeloid neoplasms with UBTF-TD, we analyzed clinical, morphologic, and immunophenotypic characteristics of 27 pediatric patients with UBTF-TD-positive myeloid neoplasm, including 21 diagnosed as AML and 6 as MDS. Our data demonstrated that UBTF-TD is frequently associated with cytopenia, hypercellular marrow with erythroid hyperplasia, and trilineage dysplasia. Blasts and maturing myeloid cells show a characteristic dysplastic feature with condensed eosinophilic cytoplasm. Blasts have a myeloid or myelomonocytic immunophenotype with a variably dim expression of CD34 and/or CD117, and except for CD7 expression lack a consistent pattern of aberrant lineage-specific antigen expression. Patients with MDS had a lower blast count in the peripheral blood (P = 0.03) and bone marrow (P < 0.001) but otherwise had no significant differences in other hematological parameters. Three patients with MDS rapidly progressed to AML in 33, 39, and 210 days from the initial diagnosis and there was no difference in overall survival between patients with MDS and AML (P = 0.18). Our data suggest that MDS with UBTF-TD is prognostically equivalent to AML with UBTF-TD and thus should be considered as a continuum of the same molecularly defined myeloid neoplasm. These collective data also provide morphologic and immunophenotypic clues that can prompt screening for UBTF-TD in patients with MDS or AML.

Keywords

Humans, Male, Child, Female, Immunophenotyping, Myelodysplastic Syndromes, Child, Preschool, Leukemia, Myeloid, Acute, Adolescent, Infant, Gene Duplication, Biomarkers, Tumor, UBTF-TD, acute myeloid leukemia, pediatric leukemia, MDS

Published Open-Access

yes

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