CWRU, MetroHealth Researchers Make Leukemia Discovery

A research team from the Gene and Cell Therapy Institute at MetroHealth and Case Western Reserve University School of Medicine has made an important discovery that could help doctors better treat leukemia, an aggressive blood cancer. The team identified key warning signs in cancer cells and developed a new "smart" drug-delivery system to overcome drug resistance, one of the biggest challenges in leukemia treatment.

^{Huiqin Bian, PhD, and Shujun Lui, PhD}

The study was led by Huiqin Bian, PhD, a postdoctoral researcher at Case Western Reserve University School of Medicine, and supervised by Shujun Liu, PhD, Professor of Medicine in the Cell and Gene Therapy Institute. Their work was published in the scientific journal RNA NanoMed and supported by the National Cancer Institute.

Many leukemia patients are treated with drugs called tyrosine kinase inhibitors (TKIs), which have dramatically improved outcomes. However, these drugs often stop working overtime because some leukemia cells learn how to survive treatment. In addition, it can be difficult to deliver drugs precisely to the cancer cells without affecting healthy cells.

To address these problems, the researchers developed tiny RNA-based drug carriers. These nanoparticles can be programmed to find specific cancer cells and deliver treatment directly to them. In this study, the team focused on leukemia stem cells – the small group of cells responsible for drug resistance and disease relapse.

The researchers discovered that resistant leukemia cells rely on a specific gene, FTO, and express high levels of a specific marker on its surface called CD133. Using this knowledge, they designed “smart” RNA nanoparticles that recognize CD133 and deliver a gene-silencing therapy that turns off FTO. In laboratory models, this approach successfully slowed the growth of leukemia cells that had become resistant to standard treatment.

“This study changes how we understand drug resistance in leukemia," Dr. Bian said. "Our RNA nanoparticles are able to seek out the most treatment-resistant leukemia cells and shut down a key gene that helps leukemia patients survive. This greatly reduced tumor growth in our models.”

Dr. Liu added that this work offers a practical path forward for more precise and effective leukemia treatments. “This approach helps solve a long-standing problem in cancer therapy – how to deliver drugs exactly where they are needed,” he said. “We are now moving toward testing these nanoparticles in patient-derived mouse models, with the goal of developing new treatment options for patients with relapsed leukemia.”