UBTF tandem duplication is a recurrent high-risk mutation in pediatric AML

March 2022 Science Nalinee Pathak

Scientists at St. Jude Children’s Research Hospital have discovered a mutation in pediatric acute myeloid leukaemia (AML)  that can be used as a biomarker to stratify high-risk patients and better guide treatment. The findings of this study were recently published in the journal Blood Cancer Discovery.

The cases of relapse in AML are complicated to treat, resulting in poor clinical outcomes. Further, genomic events associated with relapsed pediatric AML are still unknown. The researchers performed a comprehensive computational analysis of genomic data from a large cohort (136) of relapsed pediatric AML patients.

Unrecognized subtype

The analysis identified a specific type of mutation called a UBTF exon 13 tandem duplication (UBTF-TD) in 9% of relapsed AML cases. This alteration represents a new and previously unrecognised subtype in AML. Especially, UBTF-TD is more common in children than adults as UBTF-TD AMLs account for approximately 4% of all de novo pediatric AMLs. Also, this alteration is associated with poorer outcomes and an increased incidence of minimal residual disease (MRD). When expressed in primary hematopoietic cells, UBTF-TD enhanced clonogenic activity and drove a similar transcriptional program operational in UBTF-TD AMLs.

According to the corresponding author of the study,  Xiaotu Ma, PhD, St. Jude Department of Computational Biology, “This is an extremely difficult mutation to detect, so a lot of work went into developing the right algorithms. We had to develop our method from scratch. Most of the existing methodologies assume there is only one event creating these kinds of mutations but, as with UBTF-TD, that isn’t always the case. “

In conclusion, the newly identified alteration, UBTF-AD, can be used to screen high-risk AML patients and formulate new targeting therapies against altered UBTF protein.


Umeda M, Ma J, Huang BJ, Hagiwara K, et al. Integrated genomic analysis identifies UBTF tandem duplications as a recurrent  lesion in pediatric acute myeloid leukemia. Blood cancer Discov. 2022 Feb