Dr. Perlingeiro's Lab Discovers Endoglin as a Target for Acute Leukemia
To kill cancer, you need to know how it works. Obviously, that’s easier said than done, especially because there are different types of cancers that act in different ways.
But, for acute myeloid leukemia (AML) and acute B-lymphoblastic leukemia (B-ALL), the science community may be one step closer to understanding the mechanisms of development.
A new study in Blood shows that a glycoprotein on the cell surface called endoglin, also known as CD105, is a marker for the cancer stem cell in these two diseases, suggesting it plays a role in its genesis.
After discovering this feature, lead researcher Rita Perlingeiro, PhD, professor in the University of Minnesota Medical School’s Department of Medicine, Cardiovascular Division, then tested whether targeting endoglin would halt the progression of leukemia. Dr. Perlingeiro is a member of the the Lillehei Heart Institute and Lillehei Endowed Scholar. Additionally, she is a member of the Masonic Cancer Center, University of MN and collaborates with colleagues across the university as part of the Transplant Biology and Therapy research program.
“We saw a trait common among these types of cancers and wondered if blocking it or removing it from the equation would inhibit the disease,” said Perlingeiro. “It then prompted us to use an antibody to target endoglin.”
She and colleagues injected TRC105, an antibody designed to adhere to endoglin, hoping to block its activity in the cancer cells. For the mice with AML, the antibody therapy stopped the progression of cancer outright.
For those mice with B-ALL, TRC105 inhibited modestly the initiation but not the progression of disease. Perlingeiro and colleagues then demonstrated that this was because B-ALL, unlike AML, produces a lot of soluble endoglin –a version of the protein that is cleaved from the cell. Soluble endoglin acts as a decoy, limiting the ability of TRC105 to hit the cancer cells. So, when Perlingeiro’s team reduced the cancer load by treating mice with mild chemotherapy, the total amount of this decoy was reduced, and TRC105 then became effective against B-ALL.
This provides a strong rationale for testing TRC105 in patients with acute leukemias, clinical trials that Perlingeiro hopes will happen soon.
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