ASH 2021 | UBTF tandem duplications identified as a subtype-defining lesion in pediatric AML

Relapse occurs frequently in pediatric acute myeloid leukemia (AML), but the genetic alterations leading to disease recurrence remain unclear. Masayuki Umeda, MD, St. Jude Children’s Research Hospital, Memphis, TN, outlines the findings of a genomic profiling study looking at 136 cases of relapsed pediatric AML. Aside from well-characterized genetic changes involving KMT2A and NUP98, somatic mutations in UBTF were identified in 8.8% of cases. All alterations were heterozygous in-frame exon 13 tandem duplications (UBTF-TD). The prevalence and implications of UBTF alterations was further investigated, as these mutations have rarely been described in the AML literature. Using additional pediatric AML cases from previous studies, it was demonstrated that UBTF-TD AML occurred commonly in early adolescence and in those with normal karyotype or trisomy 8. UBTF-TD was also strongly associated with FLT3-ITD and WT1 mutations. Studies in cord blood CD34+ cells revealed that UBTF mutations were sufficient to induce the leukemic phenotype. Finally, the study of UBTF-TD in a larger AML cohort showed that pediatric patients with a UBTF mutation had a significantly lower 5-year survival and high levels of measurable residual disease (MRD)-positivity. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.