Acute myeloid leukemia (AML) is a cancer that affects blood cells in the bone marrow — the spongy tissue inside certain bones where new blood cells are made.
In AML patients, the bone marrow makes abnormal blood cells, which grow and divide too quickly and do not mature properly. When the abnormal cells crowd out the healthy blood cells, it can lead to infection, anemia and easy bleeding. They can also spread outside the blood to other parts of the body, such as the lymph nodes, liver, spleen and central nervous system.
While treatments such as chemotherapy can be given to a patient with AML, if the cancer relapses, their chance of survival decreases due to the limited treatment options for relapsed AML patients. A new $2.3 million grant from the National Cancer Institute is giving the Georgia Cancer Center the opportunity to understand how those cancer cells resist primary treatment and propose new treatment options that may improve patient survival.
“Acute leukemia types, including acute myeloid leukemia, account for around 4% of all cancer deaths worldwide and 6% of cancer deaths in America,” said Nahid F. Mivechi, PhD, co-leader of the Molecular Oncology and Biomarkers research program at the Georgia Cancer Center at the Medical College of Georgia at Augusta University. “AML is the second most common type of diagnosed leukemia in children and adults.”
With this multi-investigator grant, Mivechi, along with her co-principal investigator, Dimitrios Moskofidis, MD/PhD, will focus on understanding the role of heat shock transcription factors (HSFs), particularly HSF1 in acute myeloid leukemia. The protein HSF1 attaches to a specific DNA sequence inside a cancer cell during the replication process to allow the cell to make more of itself. If HSF1 is removed, cancer cells cannot replicate and will die off.
“Interestingly, our recent studies unveiled a highly novel and clinically significant role for HSF1 inhibition in metabolic reprogramming and enhancement of anti-tumor T cell immunity,” Mivechi said.
“We will be working with Dr. Jorge Cortes, director of the Georgia Cancer Center, and an internationally renowned physician for treating patients with AML, to receive blood cell samples from patients he works with,” Moskofidis said. “Our previous research projects to understand how HSFs work focuses largely on using mouse models and samples of other types of tumor cells. This is because HSFs have been shown to play a role in the replication process of many different types of tumors, not just acute myeloid leukemia.”
Also part of the research project is Huidong Shi, PhD, professor in the Department of Biochemistry and Molecular Biology at MCG and also a member of the Cancer Center’s Molecular Oncology and Biomarkers research program.
With the project, the collaborative team will investigate whether a valid approach for therapeutic interventions in acute myeloid leukemia can be based on a strategy to inhibit supportive non-oncogene addiction pathways, interfering with tumor-promoting metabolic reprogramming and improving the predicted power of anti-tumor immunity through depletion of HSF1 activity. This effort may help to find new ways to overcome key existing barriers in refractory AML management.
Kenza Mamouni contributed to this story.