By Carolyn Bernhardt, Freelance Writer
Dr. Laura Eadie’s research targets childhood leukemia with newfound precision.
As the most common cancer found in children, leukemia accounts for around 25 percent of all childhood cancer cases in Australia, where about 270 children and adolescents between infancy and 19 years of age are diagnosed each year. Luckily, Dr. Laura Eadie has always been passionate about shaping laboratory discoveries into transformed patient care. “I’m one of the lucky people who truly enjoy their job,” she says. Her research at the South Australian Health and Medical Research Institute (SAHMRI) in Australia uses genomic sequencing, laboratory models, and the pairing of FDA-approved drugs with specific leukemia profiles to advance patient care.
At SAHMRI, Eadie and her colleagues in the Leukaemia Research Group screen blood or bone marrow samples from patients all across Australia with the most common type of childhood leukemia, Acute Lymphoblastic Leukemia (ALL). “I can only imagine how harrowing it must be for parents when their child is diagnosed and undergoing treatment for ALL,” Eadie says. “Being a first-time mother to my almost-two-year-old daughter has solidified my commitment to improving survival outcomes for children with ALL.”
Eadie’s team specifically focuses on the aggressive and often deadly T-cell ALL (T-ALL), which pediatric oncologists typically treat with strong chemotherapy. But T-ALL is complex, and each patient’s disease is genomically unique. So while chemotherapy helps many children with the disease, it doesn’t work for all of them. It also has some poor, lasting effects. “In order to maximize clinical impact, we need to pair chemotherapy with a drug that targets a patient’s specific leukemia,” Eadie says.
Eadie and her collaborators use patient samples to identify each patient’s individual leukemia-causing mutations. Using sequencing data, they are able to decipher which patients harbor gene fusions that are linked to high-risk disease and poor outcomes. Gene fusions are instances where a common gene joins forces with multiple partner genes. “Through sequencing analyses, we have identified novel fusion genes and mutations in ALL patients,” she says.
Sometimes, genes fuse together in various different places, which affects different parts of both involved genes. Eadie is currently assessing a group of gene combinations where one gene joins with multiple different partner genes. She uses site-directed mutagenesis to systematically remove specific parts of the common gene. In the process, she has found that including or leaving out certain parts of the common gene—depending on where the gene combination happens—affects how well a treatment works.
As a Cancer Research Grant winner, Eadie received the PCR package from Thermo Fisher Scientific, which she and her team are using to amplify two of the brand-new gene fusions they discovered in Australian T-ALL patients. Once they successfully amplify these gene fusions, they begin site-directed mutagenesis.
Eadie next wants to clarify whether the genomic fusions her team has found are capable of causing leukemia on their own, or whether they need additional co-occurring mutations to do so. In the meantime, she and her team are also matching new and repurposed FDA-approved drugs to a patient’s specific leukemia. They make models in the lab to test and identify therapies tailored to each patient.
“Our findings will ultimately provide clinicians with an arsenal of alternative treatment options and hope for patients who have relapsed,” Eadie says. “All the information we gather will be important for determining their leukemia-causing ability and the way in which they are able to drive leukemia development. Knowing the cellular pathways that get switched on or off as a result of these novel fusions will be invaluable for identifying new custom treatment strategies physicians can use.”
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