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Under the Microscope: Refusing to Give Up on Older Patients

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, with more than 20,000 new cases diagnosed in the U.S. every year. One of the biggest mysteries of this disease is how differently it behaves in patients of different ages. When it strikes before age 25, AML is very treatable, and the vast majority of younger patients can expect to live long, full lives. For patients over 60, however, the outlook is dramatically worse: The 5-year survival rate is less than 20%, and deadly relapses are much more common.

Francine Garrett-Bakelman, M.D., Ph.D., of the University of Virginia School of Medicine, has been determined to change those outcomes ever since she first encountered AML during her hematology and oncology clinical training rotation at Weill Cornell Medicine as a medicine resident. Its effect on older patients was particularly fascinating, and frustrating, to see.

“I was humbled by the complexity of the disease and by how much patients suffer from it,” she said. “It’s one of those situations in medicine where you can really make a difference by extending survival by months or years, and helping someone through a very challenging time and treatment.”

New insights for older patients

In order to help this group of vulnerable patients live longer, Garrett-Bakelman and her team set out to decipher the role of epigenetics—changes in the expression of genes—in AML. Although our genes rarely change as we age, changes affecting the expression of genes accumulate over our lifetime and influence our health. With cancer, the relationship goes both ways: Epigenetic changes influence cancer development and the response to treatment, and cancer and its treatments can also cause epigenetic changes.

Using tissue samples from a group of older AML patients, Garrett-Bakelman and her team analyzed the expression of two genes they detected in AML: RBM47 and FBP1. They found higher expression of these genes was associated with better survival rates, even in this high-risk group.

The findings point to a possible explanation as to why some treatments work better in younger patients than older ones. At a minimum, this information may help doctors determine which older patients are most likely to benefit from available treatments. Better yet, researchers could search for new treatments that target those genes differently and may be more effective in older people.

Our goal is to use this precious material in a way that can teach us why older people developed the disease and what the biomarkers are telling us. Can they determine who should get treatment and how?

Francine Garrett-Bakelman, M.D., Ph.D.

In related follow-up studies, the team is also investigating if differences in gene expression—and the resulting differences in outcomes—could be influenced by epigenetic changes that are themselves caused by cancer therapies.

Starting out strong

Garrett-Bakelman, whose 2017 V Scholar Grant was funded by the Stuart Scott Memorial Cancer Research Fund, has been supported by the V Foundation from the start of her career, and she sees it as integral to her work. In addition to her current V Foundation grant, Garrett-Bakelman was also a Virginia Vine Team investigator in 2019.

“The funding the V Foundation offers is invaluable, especially to people like myself who are just starting out in their careers,” she said. “It has helped me focus on the science and generate exciting results I can share with others, as we strive to make progress in understanding AML.”

The future for AML

Garrett-Bakelman and her team are continuing to investigate whether epigenetic mechanisms are in fact controlling gene expression in high risk AML patients. Because of the complex interplay between genes and cancer, an answer won’t come overnight, but she is encouraged by the team’s early results.

With enough time and study, Garrett-Bakelman is confident the important questions can be answered, and eventually, patients of any age will be able to look forward to many healthy years ahead after what is, for now, a devastating diagnosis.