New Combination Therapy May Prevent Relapse of Chronic Myeloid Leukemia 

Researchers from the University of British Columbia have found a way to target the stubborn leukemic stem cells that cause lifelong risks for patients with chronic myeloid leukemia (CML)–potentially shifting the balance from treatment to a cure. 

CML is a deadly cancer that starts in the blood-forming cells of the body. Tyrosine Kinase Inhibitors (TKIs) revolutionized CML treatment by targeting the mutated protein that causes the disease. However, TKIs do not eliminate leukemic stem cells, which are a subpopulation of CML. Patients often take TKI therapy for life because leukemic stem cells can lie dormant for years and then start dividing again, causing a relapse of the disease. 

In the paper published in Cell Stem Cell, the researchers aimed to find a new way to eliminate leukemic stem cells by identifying genes important for their survival. They found high expression of a gene called Integrin-Linked Kinase (ILK) in leukemia patients, particularly in patients resistant to TKI treatment. “ILK was interesting because it has enzyme activity, so it’s really druggable,” Dr. Katharina Rothe, a postdoctoral fellow and the lead author on the paper, said. 

Treatment with a combination of TKIs and a chemical inhibitor of ILK inhibited the growth of leukemic stem cells, while healthy blood-forming stem cells were unaffected by the treatment. 

The researchers went on to use a chemically labeled leukemia cell line that allowed them to live-image the cancer in mice. When Rothe first looked at the images of mice treated with the ILK inhibitor and TKIs, she was shocked: “The combination treatment not only slowed down the progression, but the mice also had almost no detectable signal of leukemia,” she said. 10 

The ILK inhibitor appears to work by re-sensitizing the cells to TKI treatment. “The combination was highly synergistic,” Rothe said. “The ILK inhibitor seems to target pathways that the TKI is not targeting. Then when you combine them, the cells are not left with anything to survive on.” 

Many types of tumor show increased ILK expression, so Rothe believes their findings not only pave the way for a cure for CML but also may help treat other forms of cancer.