Pre-clinical models of genetically heterogeneous multiple myeloma reveal immune evasion mechanisms and predict clinical immunotherapy outcomes

The historical lack of pre-clinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers advancing therapeutic discoveries. To circumvent this limitation, we have generated fifteen genetically diverse models that developed bone marrow tumors fulfilling MM pathogenesis. Transcriptomic analysis of tumor plasma cells revealed that MYC activation regulates time to progression. Bone marrow cell composition analysis classified myeloma tumors into immune-cold and inflamed categories, which condition immune checkpoint blockade responses in mouse multiple myeloma models. Overall design: Bulk RNA sequencing from bone marrow samples isolated from multiple myeloma mouse models and RNA sequencing from sorted tumor plasma cells