UF Health Cancer Institute researchers have discovered a previously uncharacterized human gene that’s essential for the survival of aggressive T-cell lymphomas.
The findings, presented at the American Society of Hematology 67th Annual Meeting and Exposition, open the door to developing a new drug treatment that targets the gene.
“When lymphoma cells lose this gene, they cannot divide properly, so they become stuck in a critical stage of the cell cycle and eventually die,” said lead author Julian Tobon, a graduate student in the UF College of Medicine Cancer Biology Concentration. “Overall, this work identifies this gene as an entirely new regulator of lymphoma cell division and survival. We’re excited about the potential of this discovery to create a new direction for therapy development in T-cell lymphomas, which continue to have limited treatment options.”
T-cell lymphomas are a rare type of non-Hodgkin lymphomas that develop in T-cells. They often have a worse outlook with fewer treatment options than other types of lymphomas that develop in B-cells.
To identify and understand the function of the gene, which the researchers named NLP, the team used functional genetic screening, RNA sequencing and quantitative mass spectrometry-based proteomics. The team also used advanced modeling and molecular techniques to determine that the gene contains a drug-binding pocket. That means small-molecule drugs may be able to target it in the future.
Now, the researchers have ordered the top small-molecule drug candidates they predict can bind to NLP. They plan to test these compounds in T-cell lymphoma models to assess whether the compounds can halt the growth of cancerous cells. At the same time, the researchers are using mouse models to determine how the loss of the gene affects T-cell development, as well as normal mouse development.
The research team used several UF Health Cancer Institute Shared Resources, including the Flow Cytometry and Confocal Microscopy Core and the Structure-Based Drug Design Core Lab, as well as the ICBR Gene Expression and Proteomics cores and UF HiPerGator.
UF Health Cancer Institute members Rene Opavsky, Ph.D., Tobon’s faculty mentor and the study’s senior author, and Alexander Ishov, Ph.D., who contributed to the work, are co-authors.
