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Ex Vivo Modeling of Multiple Myeloma: A Novel Drug Sensitivity Screening Platform

Multiple myeloma (MM) progresses through stages, starting with precursor conditions like MGUS and smoldering MM. Key genetic events, such as chromosomal translocations involving immunoglobulin heavy-chain genes (IGH) and aneuploidy, drive this progression, with secondary alterations increasing over time. Genetic heterogeneity complicates the identification of universal MM drivers, but targeting specific mutations and translocations offers potential for better treatments for relapsed/refractory MM. A robust drug sensitivity screening platform using well-characterized primary MM patient samples is crucial for advancing these therapies.

• We present, for the first time, the feasibility of a novel ex-vivo drug sensitivity screening platform using cryopreserved primary multiple myeloma cells from a diverse range of clinically well-annotated patient samples.
  

• Cellular deconvolution reveals significant differentiation of the multiple myeloma cell population across various hematologic cell types.
  

• Additionally, differential enrichment of distinct cell types within multiple myeloma cells underscores the value of these primary samples in designing mechanism-of-action studies for novel drugs targeting relapsed/refractory multiple myeloma.