Dataset Information

Persistence of UBTF tandem duplications in remission in acute myeloid leukaemia.

ABSTRACT: UBTF tandem duplications are recurrent in adult and paediatric acute myeloid leukaemia and have been reported to be associated with a poor prognosis. Co-mutations in WT1 and FLT3 are common while morphological dysplasia is frequent. The role of UBTF-TDs in leukemogenesis is yet to be elucidated; however they have been proposed as early initiating events, making them attractive for assessment of MRD and a potential therapeutic target. We present two cases where the UBTF-TD was observed in remission and discuss the implications of these findings in the clinicobiological understanding of this emerging entity.

SUBMITTER: Harrop S

PROVIDER: S-EPMC10660390 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Persistence of UBTF tandem duplications in remission in acute myeloid leukaemia.

Harrop Sean S Nguyen Phillip C PC Byrne David D Wilson Clarissa C Ryland Georgina L GL Nguyen Tamia T Anderson Mary Ann MA Khaw Seong Lin SL Martin Michelle M Tiong Ing Soo IS Sanij Elaine E Blombery Piers P

EJHaem 20231019 4

UBTF tandem duplications are recurrent in adult and paediatric acute myeloid leukaemia and have been reported to be associated with a poor prognosis. Co-mutations in WT1 and FLT3 are common while morphological dysplasia is frequent. The role of UBTF-TDs in leukemogenesis is yet to be elucidated; however they have been proposed as early initiating events, making them attractive for assessment of MRD and a potential therapeutic target. We present two cases where the UBTF-</ ...[more]

PMID: 38024622

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Project description: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 ~4.3% of AMLs in childhood and up to 3% in adult AMLs under 60, 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.Key pointsLargest cohort of pediatric UBTF- TD in myeloid neoplasms reported to date. Use of single-cell DNA+protein sequencing technology in 3 UBTF- TD samples reveals a clonal evaluation pattern characterized by sequential acquisition of WT1 and FLT3 mutations and a more stem cell-like protein expression pattern. Pediatric MDS and AML patients with UBTF- TD alterations dysplastic features with an increase erythroid precursors. Tandem duplications in exon 9 of UBTF represent a rare but functionally equivalent subgroup of UBTF- TD myeloid neoplasms.Impact statementUBTF tandem duplications (TD) are subtype-defining genomic alterations in adult and pediatric myeloid neoplasms. Here, we provide a comprehensive characterization of the largest cohort of pediatric UBTF -TD cases to date, including the recognition of additional UBTF alterations that mimic the exon 13 duplications in pediatric AML.

Dataset Information

Persistence of UBTF tandem duplications in remission in acute myeloid leukaemia.

Publications

Persistence of <i>UBTF</i> tandem duplications in remission in acute myeloid leukaemia.

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