UBTF tandem duplication defines High-risk Pediatric Acute Myeloid Leukemia

Genomic profiling of relapsed pediatric AML demonstrated an increase in KMT2A and NUP98 rearrangements when compared to de novo pediatric AML, as well as an increase in WT1 mutations. Notably, we identified recurrent (9% of relapse cohort) exon 13 duplications in UBTF in pediatric AML cases that previously lacked known driver alterations. These UBTF-tandem duplication (TD) pediatric AMLs occur in approximately 4% of all pediatric AMLs and are less common in adult AMLs, are associated with normal karyotype or trisomy 8 cytogenetic abnormalities, co-occur with WT1 and FLT3-ITD, have an expression profile similar to NUP98-NSD1 and NPM1 mutant AMLs and are independently associated with poor outcome.EGA study EGAS00001005760