Research reveals high-risk subtype of relapsed pediatric AML

Date:
February 17, 2022
Source:
St. Jude Children's Research Hospital
Summary:
Scientists have found a previously overlooked mutation in a
subtype of pediatric leukemia that has implications for identifying
high-risk patients.



FULL STORY ==========================================================================
When acute myeloid leukemia (AML) relapses, it is more difficult to
treat and outcomes are dismal. Scientists at St. Jude Children's Research Hospital have discovered a mutation in pediatric AML that physicians can
use to identify high-risk patients and better guide treatment. A paper
on the work appeared today in Blood Cancer Discovery, a journal of the
American Association for Cancer Research.


==========================================================================
"We started broadly because it was clear that we didn't have a deep enough understanding about why kids with AML relapse in the first place," said
co- corresponding author Jeffery Klco, M.D., Ph.D., St. Jude Department of Pathology. "We have a number of clinical trials at St. Jude for relapsed
AML, so that gave us access to a large cohort of samples, and that is
where the collaboration with our colleagues in Computational Biology
became really beneficial to help us analyze the genetics.

"It became clear early on that there was a group of cases who had curious alterations in this gene UBTF, which had really only been superficially considered in the past," Klco said.

A new high-risk subtype The researchers evaluated the genomics of 136
St. Jude patients treated for relapsed AML. A specific type of mutation
called a UBTF exon 13 tandem duplication (UBTF-TD) occurs in 9% of
relapsed pediatric AML. This represents a significant and previously unrecognized subtype.

UBTF-TD AML is more common in children than adults. It is also associated
with poor outcomes and an increased incidence of minimal residual disease (MRD). MRD refers to cancer cells that persist in small numbers after
initial treatment, often giving rise to recurrence of the cancer.

Genetic analysis The genomics of AML have been studied for many years,
but this mutation has been mostly overlooked or undetected in previous
work. Researchers at St. Jude developed the computational approaches
to identify this, and potentially similar mutations, in AML and other
cancers.

"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," said co-corresponding author Xiaotu Ma, Ph.D., St. Jude Department of Computational Biology. "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." "Now that we know what
we're looking for and how to find it, we can readily incorporate it into clinical genomics," Ma said.

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

========================================================================== Story Source: Materials provided by
St._Jude_Children's_Research_Hospital. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Masayuki Umeda et al. Integrated genomic analysis identifies
UBTF tandem
duplications as a recurrent lesion in pediatric acute myeloid
leukemia.

Blood Cancer Discovery, 2022 DOI: 10.1158/2643-3230.BCD-21-0160 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220217102047.htm

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