City of Hope study published in Nature Medicine reports on promising new drug to fight chronic myelogenous leukemia

March 5, 2018
Letisia Marquez
[email protected]
In preclinical research, the drug called miristen – developed at City of Hope – appeared to eradicate the disease
DUARTE, Calif. — City of Hope scientists and doctors may have discovered a more effective treatment for patients with chronic myelogenous leukemia (CML) using a drug that was developed at the institution to eradicate CML stem cells, according to a study published today in Nature Medicine.

CML is a type of cancer that starts in the blood-forming cells of the bone marrow and invades the blood. Although there are first-line drug treatments to induce long-term remission in CML patients, called tyrosine kinase inhibitors (TKI), leukemia stem cells, which initiate and maintain the disease, frequently persist; these cells can result in a relapse of the disease. TKIs are also expensive and a patient with CML needs to take the drug for life.

City of Hope researchers aimed to find a treatment for CML that was effective enough for people to stop using TKIs. In their quest to find a cure for the disease, the team tested a drug called miristen. Developed at City of Hope, miristen targets one type of a microRNA that is expressed in leukemia stem cells, known as miR-126, and researchers believed to be important for self-renewal and persistence of stubborn leukemia stem cells.

Led by Bin Zhang, M.D., and Ph.D., an associate research professor in the Department of Hematologic Malignancies Translational Science, and Guido Marcucci, M.D., chair and professor of the City of Hope Department of Hematologic Malignancies Translational Science, and director, Gehr Family Center for Leukemia Research, the team tested various combinations of miristen and other drugs in mouse models with CML. These included miristen with TKIs and without them.

The best results were seen in those treated with miristen and a TKI. Transplantation of the bone marrow cells collected from those treated with miristen and TKI resulted in no sign of leukemia in the healthy recipient mice, meaning all leukemia stem cells were eliminated. The researchers believe that miristen simply makes the TKIs more effective in killing the leukemia stem cells.

“This is could be a major breakthrough for people who are in remission for CML because there is always a concern that the disease will come back if TKI treatment is stopped,” Zhang said. “Miristen could be the drug that sends the disease into permanent remission.”

Zhang and Marcucci noted that their research also unearthed another important finding for CML that was key to the treatment’s success. The team discovered that endothelial cells in the blood vessels of a person’s bone marrow — where CML begins — contain high levels of miR-126. These endothelial cells transfer miR-126 to leukemia stem cells, essentially feeding the cancer what it needs to survive and relapse. The researchers hypothesized that to eliminate CML, miristen had to lower miR-126 in both the leukemia stem cells and the endothelial cells; testing of their idea showed that it does.

“What we have discovered is how the microenvironment surrounding the leukemia stem cells supports them and how you need to target miR-126 in the leukemia stem cells and the microenvironment to completely eradicate the disease,” Marcucci said. “Our current study showed these findings may also apply to other types of leukemia.”

City of Hope is currently working on bringing miristen from the laboratory to the clinic for treatment in patients.
About City of Hope
City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 49 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community practice sites throughout Southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and numerous breakthrough cancer drugs based on technology developed at the institution.
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