Scientists Identify Potential Target for Treating Acute Myeloid Leukemia Mutation

researcher with microscope

Acute myeloid leukemia (AML) is driven by mutations that occur in numerous combinations, but their effects are often studied in the absence of other mutations. New cancer research from Versiti Blood Research Institute examines how two common, co-occurring mutations (Npm1c and cohesin) influence the biology of the disease. Their findings, published in Leukemia, reveal that targeting the Dock1 gene decreased the growth of AMLs containing both of these mutations.

Initially, the team was surprised to discover that the Npm1c and cohesin combination did not result in decreased time to AML formation, especially because these mutations co-occur in 5-15% of human AMLs. “However, we did learn that the genes that were being expressed in the leukemias containing both mutations were quite different. Therefore, a new set of potential targets for therapy were uncovered, making it possible to target leukemias that contained both mutations. We chose to focus our studies on Dock1, as high expression has been associated with AML in humans,” said Versiti's Alison Meyer, PhD.

Leukemia cells within an individual patient can have between 5-15 mutations that occur in a variety of combinations. This is why a one-size fits all approach to therapy is unlikely to significantly improve AML outcomes. Dr. Meyer said although it can be daunting to study all of the different combinations of mutations that occur in humans, it is important for researchers to understand how changes in AML biology can lead to the discovery of life-saving targeted treatments.

“The development of targeted therapies is necessary to increase survival in AML patients," said Dr. Meyer. "My advice for future investigators is to dig a little deeper if they originally do not see what they expected to see. There may be something very interesting hiding under the surface of an initially disappointing result.”