Discovery of Key Proteins Offers New Treatment Hope for Acute Lymphoblastic Leukemia

Key Insights

• Researchers identified two proteins, ERG and c-MYC, critical for the development of B-cell acute lymphoblastic leukemia, offering new therapeutic targets.
• Targeting POL I, a gene essential to ribosome biogenesis controlled by ERG and c-MYC, effectively killed leukemia cells and stopped their growth in preclinical models.
• The study highlights the potential of POL I inhibitors as a novel therapeutic approach for aggressive acute lymphoblastic leukemia, with plans for future clinical trials.

Researchers from WEHI and the Peter MacCallum Cancer Centre have identified two proteins crucial for the development of B-cell acute lymphoblastic leukemia, opening new avenues for potential treatments. The study, published in Science Advances, demonstrated that targeting these proteins could effectively kill leukemia cells and halt cancer cell growth in laboratory settings.

Identifying Key Proteins in Leukemia Development

Associate Professor Ashley Ng, a lead author on the paper, highlighted the urgent need for new therapeutics, noting that 50% of Australian patients with blood cancers relapse after initial chemotherapy and develop resistance to further treatments. The research focused on understanding how leukemia cancers behave and what drives their growth. The team identified ERG and c-MYC as master regulators of critical pathways within leukemia cells.

Targeting Ribosome Biogenesis

The research team narrowed their focus to ribosome biogenesis, a pathway essential for protein production. By targeting POL I, a key gene in this pathway controlled by ERG and c-MYC, researchers were able to disrupt leukemia cell growth. Dr. Kira Behrens, the first author of the study, noted that inhibiting POL I with specific inhibitors led to the death of leukemia cells and the cessation of their growth in preclinical models.

Collaboration and Future Clinical Trials

The study also involved collaboration with Associate Professor Elaine Sanij from St. Vincent’s Institute of Medical Research, whose work focuses on targeting POL I and ribosome biogenesis in cancer therapy. According to Assoc Prof Sanij, the findings indicate that aggressive acute lymphoblastic leukemia exhibits a form of addiction to ribosome production, rendering it sensitive to POL I inhibitors.

Professor Rick Pearson from the Peter MacCallum Cancer Centre indicated plans to mimic the study in a future clinical trial. The team hopes this research will translate into successful clinical trials and potentially offer doctors a new treatment option for patients with acute lymphoblastic leukemia.