About 500 children are diagnosed with AML each year in the United States. While AML is much more common in adults, it is the second most common cancer in children. Five year survival rates range from 65-75%. The management and diagnosis of pediatric AML continues to transform and improve. New research presents options for treatment based on insight gathered from genetic changes. Testing on genomic sequencing can help define the specific details in a patient’s treatment plan. 

Adult AML and pediatric AML can react differently to these genomic sequences. “Myeloid tumors in children are commonly caused by a different set of mutations than those seen in adults, but the genetics of pediatric myeloid tumors are not well understood.” Adult AML is a result of decades of acquiring genetic mutations. Pediatric AML is caused by fewer but more destructive events.

The Klco lab at St. Jude Children’s Research Hospital is focused on finding and understanding myeloid tumors in children. The UBTF mutation has recently been researched at the lab. While it is rare in adults, it is very prevalent in children. “It is important to look for the UBTF tandem duplication in kids at diagnosis to predict whether they have an increased risk of experiencing a relapse.”

AML relapses occur in about 20% of cases. It is not yet known the specific reasons why some children relapse and others don’t. It is very beneficial to identify any genetic mutations early in the treatment phase. UBTF-TD is now one of the top mutated sequences in pediatric AML. This specific data predicts poor outcomes in patients. Previously this mutation was difficult to detect. New algorithms created by Dr. Ma at St. Jude’s, have provided researchers with the right skills to detect UBTF mutations. “Having a new mutation to focus on in these cases is really exciting because in the future it might be possible to target UBTF-TD mutations therapeutically.”

The next goal for researchers is to find out why the UBTF mutations lead to leukemia. “Once we get a better understanding of what pathways are altered when they’re in the presence of a UBTF tandem duplication, we will be able to understand, or at least start thinking, about potential therapeutic options. But first, we need to understand how it is working.” said Dr. Klco.

The specific details of the UBTF mutation testing:

• 136 relapsed pediatric patients were tested.
• 13 TD (tandem duplications) found in 9% of UBTF cases.
• UBTF-TD AMLs commonly have normal karyotype or trisomy 8 along with WT1 mutations or FLT3-ITD. 
• UBTF-TD AMLs account for approximately 4% in the newly diagnosed cases.
• Less common in adults.
• Associated with poor outcomes and MRD (measurable residual disease) positivity.
• This data establishes UBTF-TD as a new and recurrent mutation in AML.

“Clinical genomics can be used to screen for UBTF-TD mutations in AML to help identify high-risk patients. The findings also open up new areas of investigation, including finding ways to target the protein created by UBTF-TD and determining how the aberrant peptide contributes to leukemia.”