Science
Advancing acute myeloid leukemia research through epigenetics
August 31, 2020     

Understanding the genetic diversity of acute myeloid leukemia 

C.L. Beach, executive director for MDS & AML

C.L. Beach, executive director for MDS & AML, Hematology/Oncology Clinical Research and Development

Over the past few decades, great strides have been made in our understanding of how changes in the genes inside bone marrow cells can progress into certain blood cancers, such as acute myeloid leukemia (AML), one of the most common acute leukemias in adults. Deeper insights into these gene changes tell us more about the diverse nature of this rare disease, how AML can progress and which treatments might be effective.

“AML can develop either in a healthy person or in those with a predisposing disease of the myeloid cells called myelodysplastic syndrome, also known as MDS,” said C.L. Beach, executive director for MDS & AML, Hematology/Oncology Clinical Research and Development at BMS. “Over time, about one-third of people with MDS develop AML, and this risk can depend on the type of MDS a person has at the time of diagnosis.”

AML is a fast-moving leukemia that starts in the bone marrow and may require immediate treatment. While many patients will achieve remission, about half will relapse within one year. Optimizing treatment, especially of older people with AML with co-morbidities, has remained a challenge for researchers.   

The role of hypomethylating agents in AML treatment    

 

The study of epigenetics involves evaluating external changes to DNA that turn genes “on or off.” These modifications do not alter the DNA sequence, but they do affect how cells interpret genes.

DNA methylation is one type of epigenetic signaling tool that involves the addition of a methyl group to part of the DNA molecule, preventing certain genes from being expressed. Excessive methylation of certain tumor suppressor genes is linked to the development of some cancers, like AML.

“We’ve seen great potential with a type of epigenetic therapy called hypomethylating agents, or HMAs, which inhibit DNA methylation and have gained traction in AML treatment,” said Beach.

Beach described how HMAs work differently than standard treatments for AML and other cancers:

“Treatment with intensive chemotherapy has historically been the approach to treating blood cancers and some solid tumors, using a maximum dose with the hope of altering the course of the disease and keeping side effects at a generally manageable level,” he said. “Alternatively, HMAs work in a different way. Instead of killing the cell, they alter the signaling process by facilitating the re-expression of genes, thus helping to elicit the proper effect on the cell. With this type of therapy, we’ve learned that repeated exposure with low doses leads to clinical benefit for AML patients.”

Looking ahead, AML remains a hard-to-treat blood cancer, and options are needed that will increase overall survival for people living with this persistent disease. As epigenetic modifications in various malignancies continue to be evaluated, HMAs may play an increasing role in the treatment of AML. 


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