Researchers led by Ludwig Harvard’s Constantine Mitsiades used CRISPR genome editing to explore the distinct molecular dependencies of cells that give rise to the incurable plasma cell cancer multiple myeloma (MM) in the hope of finding targetable vulnerabilities that are specific to this cancer. They reported in a Nature Cancer paper in May their characterization of the molecular dependencies specific to the lineage of cells that gives rise to MM as compared to those of hundreds of non-MM cell lines. Constantine and his colleagues identified 116 genes—some known to be linked to the plasma cell cancer, many others not—that more significantly support the fitness of MM cells than that of other cancers. Most are not among the top amplified, overexpressed or mutated in MM, and they include genes that encode proteins that regulate gene expression, such as transcription factors and chromatin modifiers, components of the endoplasmic reticulum—a cellular organelle involved in the processing and chemical modification of newly made proteins—regulators of cellular metabolism and signaling molecules. Their functional genomics approach, the authors noted, identified several potential drug targets that might not have been noticed via typical genomic, transcriptional or epigenetic profiling analyses.
Genome-scale functional genomics identify genes preferentially essential for multiple myeloma cells compared to other neoplasias
Nature Cancer, 2023 May 26