Study Finds Potential Therapeutic Target for Pediatric Acute Myeloid Leukemia

A new study by Nemours Center Children’s Health System found a gene expressed in children with acute myeloid leukemia (AML) that could serve as a new immunotherapy treatment target.

The study outlines the process and potential path for new immunotherapy drugs that improve survival and reduce treatment-related toxicity in children with AML. Leukemia is the most common cancer in children and teens, and AML accounts for nearly one-fourth of those cases.

“Using genomic sequencing data, we identified novel targets for children’s cancer and worked with collaborators to engineer new therapies for children with AML, rather than repurpose drugs from the adult cancer realm that don’t work well in children,” said senior study author E. Anders Kolb, MD, director of Nemours’ Center for Childhood Cancer Research, in a press release.

The researchers obtained genomic data from more than 2000 pediatric patients with leukemia to identify associated gene variants. Through genomic sequencing, they found that the gene mesothelin (MSLN) is abnormally expressed in more than one-third of childhood and young adult AML cases, but was absent in normal bone marrow cells, according to the study.

The researchers chose new immunotherapy drugs that would target MSLN to test in cell lines and animal models to further measure pre-clinical effectiveness of leukemia therapies. Anetumab ravtansine (Bayer) and newer compound anti-MSLN-DGN462 (ImmunoGen) were tested, with each drug producing potent destruction of leukemia cells, according to the study.

“We are working to show a proof of principle that we can create custom therapies for pediatric malignancies and turn the drugs we’re testing in the lab into clinical trials,” said Sonali P. Barwe, PhD, the study’s co-lead author and head of the Preclinical Leukemia Testing Laboratory in Nemours’ Center for Childhood Cancer Research, in the press release.

REFERENCE

Study finds potential therapeutic target for pediatric acute myeloid leukemia. Nemours. Published May 3, 2020. Accessed May 6, 2021. http://nemours.mediaroom.com/media-releases?item=122879