Analysis Uncovers Brentuximab Vedotin Susceptibility Markers for CD30-Positive PTCL

In CD30-positive peripheral T-cell lymphomas (PTCLs), analysts used genome-wide, loss-of-function CRISPR screening to identify markers of susceptibility to brentuximab vedotin therapy. Their research was presented in Leukemia.

“Aside from CD30 expression, the molecular mechanisms that determine brentuximab vedotin efficacy, in particular sensitization, remain largely unexplored,” wrote Masao Nakagawa, MD, PhD, of the Faculty of Medicine at Hokkaido University in Sapporo, Japan, with coauthors.

The analysis team’s goal with screening was to pinpoint which PTCL cell-intrinsic molecules are involved in susceptibility to brentuximab vedotin, an anti-CD30 antibody and microtubule inhibitor conjugate. They performed next-generation sequencing of cell line genomic DNA, from which their model-based analysis identified 18 sensitizing genes and 15 genes which brought brentuximab vedotin resistance with knockout.

“TNFRSF8, also known as CD30, was ranked as the most enriched gene in our screen. This result indicated the reliability of this screening since TNFRSF8 is the target gene of brentuximab vedotin,” the coauthors wrote.

Their findings further pinpointed anaphase promoting complex subunit 15 (ANAPC15) and the MAD2L1 binding protein as associated with brentuximab vedotin sensitivity.

Reference

Suto K, Takei N, Yokoyama K, et al. Genome-wide CRISPR screen identifies MAD2L1BP and ANAPC15 as targets for brentuximab vedotin sensitivity in CD30+ peripheral T-cell lymphoma. Leukemia. Published online October 21, 2024. doi:10.1038/s41375-024-02441-1