Study: Genetic Mutations Link Could Lead to New AML Treatment Strategy

Researchers at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James) and Memorial Sloan Kettering Cancer Center (MSK) have found a connection between two genetic mutations in a subtype of acute myeloid leukemia (AML) — a finding that could lead to new ways to treat this aggressive blood cancer.  

Published in the Journal of Clinical Investigation, the study — which involved mouse models of human AML as well as human AML patients — focused on mutations (abnormal changes) in two genes, TP53 and TET2, that cooperate to transform blood cells and play a key role in AML development. 

By examining groups of AML patients from the OSUCCC – James and MSK, the scientists saw that 10% of AML patients who have TP53 changes also have TET2 changes — an AML subtype that has very poor clinical outcomes.  

The researchers also found that both mice and humans with this subtype displayed high amounts of a molecule called CD155 on their cancer cells, and that using antibodies to block the CD155 molecule helped the immune system destroy the TP53/TET2 cells. This improved patient survival and pointed toward a possible new treatment strategy for patients with this AML subtype. 

Authors of the study include Pelotonia-funded researchers Rosa Lapalombella, PhD, co-leader of the Leukemia and Hematologic Malignancies (LHM) Program at the OSUCCC – James; 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. 

Read the full story on the OSUCCC – James news page here.