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Using the novel method of single-sell RNA sequencing, recently established by the Institute of Immunobiology at MFZ, KSSG, and our experience and knowledge about proteasome inhibitor resistance of myeloma plasma cells in vitro, we shall use the MFZ start-up research funding to initiate a research line in our laboratory that aims to characterize the changes in the myeloma plasma cells in vivo that drive the resistance to proteasome inhibitors in multiple myeloma and further explore and characterize the most prominent findings. This shall be done in parallel by profiling primary myeloma plasma cells from patients responding or non-responding to proteasome inhibitor based therapy as well as by profiling of the human myeloma plasma cells growing in immunodeficient mice bone marrow and progressing after the treatment with proteasome inhibitor.