Protein Imbalance Can Result in Pediatric Leukemia
The activation of the STAT5 protein linked to acute lymphoblastic leukemia.
The activation of a protein may lead to the development of a common pediatric leukemia, according to a study published by Nature Immunology.
The authors reported that the activation of the STAT5 protein results in competition that can cause acute lymphoblastic leukemia (ALL), suggesting that a drug that prevents activation and restores the balance of the proteins could lead to a better treatment for ALL.
Blood cancers account for approximately 10% of newly diagnosed cancers, with pediatric ALL responsible for 3 out of 4 new cases of the disease. ALL occurs when the body creates too many immature lymphocytes, and is common among very young children.
Previous studies have shown that genetic mutations drive leukemia, like many other cancers. In the new study, the authors found that activating the STAT5 protein in mice always led to leukemia development.
"The major outcome of this story is that a signature emerged from looking at the level of activated proteins compared to other proteins that's very predictive of how a patient will respond to therapy," said researcher Seth Frietze, PhD. "That's a novel finding. If we could find drugs to target that activation that could be an incredibly effective way to treat leukemia."
A data analysis conducted by Dr Frietze supported the finding that the ratio of activated STAT5 to IKAROS in patients throws off the protein balance and leads to leukemia, according to the study.
The authors used an approach that included mouse models and patient samples, which were analyzed through high-throughput DNA sequencing, epigenetic, and proteomic analysis.
Patient with a high ratio of imbalanced proteins — STAT5 to IKAROS or NF-kB – were observed to have worse disease prognosis, according to the study.
“Tumor sequencing is currently being used to both risk stratify patients and provide novel therapeutic targets. However, the ways in we are able to use that sequencing information is still limited,” Dr Frietze said. “This study provides a new way to risk stratify patients, identifying those who are at higher risk or relapse and may therefore need more intense therapy to cure their disease."
This protein signature could be used to predict prognosis among patients with ALL to determine the best treatment approach. Avoiding ineffective treatment not only prevents pediatric patients from experiencing harsh side effects, but also reduces costs associated with cancer drugs and healthcare utilization.
In the future, the creation of drugs that normalize protein balance could be used to prevent ALL among high risk children.