Researchers Identify Approach to Overcome Drug Resistance in Leukemia

Researchers from the Gene and Cell Therapy Institute at MetroHealth and Case Western Reserve University School of Medicine have identified new biomarkers and treatment strategies that may help predict and overcome drug resistance in chronic myeloid leukemia (CML), a blood cancer that affects thousands of patients each year.

^{Yanhong Tan, PhD, and Shujun Liu, PhD}

The study, led by research scientist Yanhong Tan, PhD, and supervised by Shujun Liu, PhD, Professor of Medicine in the Cell and Gene Therapy Institute and at CWRU, was published in the journal Cell Death & Disease and funded by the National Cancer Institute.

CML is typically treated with tyrosine kinase inhibitors (TKIs), oral targeted cancer drugs that have transformed patient outcomes. However, many patients do not respond fully, and others must remain on treatment for life because the cancer becomes resistant.

The MetroHealth research team discovered that some leukemia cells survive treatment not because of genetic mutations, but due to changes in how RNA is regulated. The study identified a new biological 'shield' – made of specific RNA molecules and growth signals – that helps cancer cells survive and resist targeted therapy. This "non-genetic" resistance helps explain why some patients relapse even when no new mutations are found.

Importantly, the researchers showed that drugs targeting this pathway can eliminate these resistant leukemia cells. The identified RNA molecules may also serve as biomarkers to predict which patients are most likely to respond well to therapy and potentially achieve long-term remission without ongoing treatment.

"These findings provide a new framework for understanding and overcoming drug resistance in leukemia," said William Tse, MD, Executive Director of the Gene and Cell Therapy Institute. "Dr. Liu and Dr. Tan were instrumental in designing and executing this work. This study opens the door to new treatment strategies for patients whose disease does not respond to current therapies."

Tragically, Dr. Tan passed away two weeks after the study was published. Dr. Liu and members of the research team honor her dedication, scientific rigor and commitment to advancing cancer research, which were critical to the success of this work.