Protein Signature Highly Predictive of Acute Lymphoblastic Leukemia

Findings could help improve treatment efficacy for patients with ALL.

The activation of a signature protein causes competition among other proteins, resulting in the development of acute lymphoblastic leukemia (ALL), a recent study found.

In the United States, blood cancers account for nearly 10% of all newly diagnosed cancer cases. Childhood ALL accounts for 3 of 4 causes of leukemia and is most common in children under age 5.

Prior research shows that certain genetic mutations that are commonly found in leukemia play a role in driving the disease. In a new study published in Nature Immunology, investigators found that forcing the activation of the protein STAT5 in mice always produced leukemia.

“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 investigator Seth Frietze. “That’s a novel finding. If we could find drugs to target that activation that could be an incredibly effective way to treat leukemia.”

Corresponding author Michael Farrar led a team of scientists who used an innovative methodology that combines unique mouse models and patient samples in combination with high-throughput DNA sequencing, epigenetic, and proteomic analysis.

The results of the study showed that patients who had a high ration of imbalanced proteins—–STAT5 to IKAROS or NF-kB––had a significantly worse prognosis.

The findings indicate that an imbalance of 2 imposing transcriptional programs drives ALL and suggests that restoring the balance of these pathways may inhibit ALL, according to the authors.

“Tumor sequencing is currently being used to both risk stratify patients and provide novel therapeutic targets,” Frietze said. “However, the ways in [which] we are able to use that sequencing information is still limited. This study provides a new way to risk stratify patients, identifying those who are at higher risk of relapse and may therefore need more intense therapy to cure their disease.”