Understanding Drug Resistance in Multiple Myeloma: Insights from Tomas di Domenico

Tonight, I watched Tomas di Domenico from the National Cancer Research Center in Spain present at London Calling 2024 on “An (epi-)genomics analysis of drug resistance in multiple myeloma.” Di Domenico explained how multiple myeloma affects the bone marrow and thickens the blood. Multiple myeloma also causes bone issues. There are several treatments and a standard of care. di Domenico is interested in resistance to newer therapies, including immunotherapy. Myeloma patients undergo cycles of treatment and resistance. Drug resistance work has been performed to characterize point mutants. The R10 and P2 Solo promised ONT sequencing to learn about multi-drug resistant cell lines. The team sequenced several resistant cell lines, producing the 20X coverage baseline. The research team compared methylation signals. The methylation signals and differential methylation data seemed successful. Ongoing projects are using samples from patients undergoing immunotherapy treatments. Obtaining one microgram of DNA was sometimes a challenge. di Domenico also confessed they had to perform “Nanopore magic” by removing the sample/library and loading a new flow cell! The research team continues improving the sequencing of these clinical samples and learning about the development of resistance mechanisms.

How can drug resistance in multiple myeloma patients evolve? AI-generated image.