Health
Studies reveal a high-risk subtype of recurrent pediatric AML-ScienceDaily
When acute myeloid leukemia (AML) recurs, it becomes more difficult to treat and the outcome is disastrous. Scientists at St. Jude Children’s Research Hospital have discovered mutations in pediatric AML that doctors can use to identify high-risk patients and better guide their treatment.A paper on the work was published today Discovery of blood cancerJournal of the American Cancer Society.
“It was clear that we didn’t fully understand why children with AML recur in the first place, so we started broadly,” said co-author Jeffrey Kurco, MD, Pathology, St. Jude. “Because of the many clinical trials in St. Jude for recurrent AML, we have access to a large cohort of samples, and collaborative research with colleagues in computational biology has been very helpful in genetic analysis.
“It became clear early on that there was a group of cases with strange changes in this gene. UBTFThis was actually only superficially considered in the past. “
New high risk subtype
The researchers evaluated the genomics of 136 St. Jude patients treated for recurrent AML.A specific type of mutation called UBTF Exxon 13 tandem reproduction (UBTF-TD) occurs in 9% of recurrent pediatric AML. This represents an important and previously unrecognized subtype.
UBTF-TD AML is more common in children than in adults. It is also associated with poor outcomes and an increased incidence of minimal residual disease (MRD). MRD refers to cancer cells that last only a few times after the first treatment and often cause the recurrence of the cancer.
Genetic analysis
Although the genomics of AML have been studied for many years, this mutation has been largely overlooked or undetected in previous studies. Researchers at St. Jude have developed a computational approach to identify potentially similar mutations in AML and other cancers.
“This is a mutation that is very difficult to detect, so a lot of work was spent developing the right algorithm. We had to develop the method from scratch,” said the co-author. Xiaotu Ma, Ph.D., St. Jude Department of Computational Biology. “Most existing methodologies assume that only one event creates these types of mutations, UBTF-TD, not always. “
“Once we know what we are looking for and how to find it, we can easily incorporate it into clinical genomics,” Ma said.
Can be screened using clinical genomics UBTF-A TD mutation in AML that helps identify high-risk patients. This process is already underway at St. Jude.The findings also open up new areas of study, including methods of findings targeting the proteins produced by. UBTF-Determine how TDs and abnormal peptides contribute to leukemia.
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