Toward more effective treatment for leukemia

The discovery of a protein signature that is highly predictive of leukemia could make way for new and more effective therapeutics, according to a new study.

The University of Vermont study revealed that the activation of a protein known as STAT5 causes competition among other proteins that leads to acute lymphoblastic leukemia (ALL). If a drug could be developed to prevent the initial activation of STAT5 and restore the natural balance of proteins, ALL could potentially be treated more effectively.

The team found that by forcing the activation of STAT5 in mice (constitutively activated alleles forced by the researchers) 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 researcher 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 10 researchers that employed an innovative methodology that combines unique mouse models and patient samples in combination with high-throughput DNA sequencing, epigenetic and proteomic analysis. The result was that patients with a high ratio of imbalanced proteins (STAT5 to IKAROS or NF-kB) had far worse prognosis.

Frietze put the finding in perspective by explaining that "tumour 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. 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."

The study is published in the journal Nature Immunology.