Molecular network may be therapeutic target for AML
Researchers at the OSUCCC – James have identified a self-feeding “vicious circle” of molecules that keeps acute leukemia cells alive and growing. Their findings suggest a new strategy for treating acute myeloid leukemia (AML) by targeting this molecular network and lowering the amount of a protein called KIT.
The study describes a network of protein and microRNA molecules that, when imbalanced, contributes to increased KIT expression and favors leukemia development. The researchers also were able to target this network with therapeutic drugs.
“We now understand the mechanism responsible for high KIT expression in AML cells, and we believe that targeting that mechanism and reducing KIT levels will prove a more effective therapy than the current standard of care,” says study leader .
More than 80 percent of AML cases show elevated KIT expression. Doctors treat AML with standard chemotherapy, but drugs that target and block KIT activity are being tested in clinical trials. These agents, tyrosine kinase inhibitors, bind to the protein and stop disease progression, but they can lose their effectiveness when new mutations that arise from the disease alter the protein.
“Our study suggests that the amount of KIT protein in cancer cells is as important as its activity, and we discovered that the amount of the protein is controlled by a circular network of molecules that has many points of entry,” says senior co-leader Ramiro Garzon, MD. “These findings provide a strong rationale for developing drugs that target the components of this network rather than focusing on the activity of KIT alone.”
Published in the journal Cancer Cell.