COLUMBUS, Ohio – Researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and Memorial Sloan Kettering (MSK) Cancer Center in New York have found a link between two genetic mutations in a subtype of acute myeloid leukemia (AML), which could lead to new ways to treat the disease. The study, published in the Journal of Clinical Investigation, found a link between mutations in the TP53 and TET2 genes, which transform blood cell formation and play a role in AML development. “Altogether, the findings show a leukemia-promoting link between TET2 and TP53 mutations and highlight therapeutic strategies to help patients overcome the immunosuppressive actions of this adverse subtype of AML,” said one of the study’s co-corresponding authors Rosa Lapalombella, PhD, co-leader of the Leukemia and Hematologic Malignancies (LHM) Program at the OSUCCC – James. Study design and findings The study looked at mouse models of human AML as well as human patients, and found genetic parallels in this AML subtype. By studying two groups of AML patients from different institutions, the researchers identify that 10% of TP53-mutant AML cases carry a concurrent TET2 mutation and are associated with extremely poor clinical outcomes. They found that mice with combined TP53 and TET2 mutations develop aggressive acute leukemia that closely resembles human AML, providing a valuable model for comparison with human patients. Among their other findings were: • Preclinical models and AML patients with TP53/TET2 mutations had higher immune signaling in cancerous cells that could lead to leukemia • Preclinical models with TP53/TET2 mutations had more suppressor cells that stopped T cells from fighting cancer • Preclinical models and AML patients with TP53/TET2 mutations had high levels of CD155 on cancerous cells. The study also found that using antibodies to block the CD155 ligand boosted the ability of the immune system’s natural killer cells to destroy TP53/TET2-mutated AML cells, reducing leukemia burden, prolonging survival in TP53/TET2 preclinical models and pointing toward a possible treatment strategy for human patients.  Study authors Other co-corresponding authors for the study – supported in part by funds from Pelotonia, the community and cycling event that raises money for cancer research at Ohio State – were Bradley Blaser, MD, PhD, a member of the LHM Program; and Omar Abdel-Wahab, MD, chair of the Molecular Pharmacology Program at MSK. The study’s first author was Pu Zhang, PhD, a former PhD student and Pelotonia Scholar in Hematology at Ohio State who is now a postdoctoral fellow at MSK.  Ann-Kathrin Eisfeld, MD, director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at the OSUCCC – James, and members of the Bloomfield Center, provided clinical data for this study. To learn more about cancer treatment and clinical trials at the OSUCCC – James, visit cancer.osu.edu or call 1-800-293-5066. Media Contact: Mary Ellen Fiorino, Mary.Fiorino@osumc.edu