Resource and Technical AdvanceIn-Press PreviewHematology Open Access | 10.1172/jci.insight.177300
1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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1Division of Hematology Oncology, University of Pennsylvania, Philadelphia, United States of America
2Jackson Laboratory, Bar Harbor, United States of America
3Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, United States of America
4Stem Cell and Xenograft Core Facility, University of Pennsylvania, Philadelphia, United States of America
5Division of Hematology Oncology, University of Pennsylvania, Philadephia, United States of America
6Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America
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Published May 7, 2024 - More info
Multiple myeloma is a largely incurable and life-threatening malignancy of antibody-secreting plasma cells. An effective and widely available animal model that recapitulates human myeloma and related plasma cell disorders is lacking. We show that busulfan-conditioned hIL-6 transgenic NSG mice (NSG+hIL6) reliably support the engraftment of malignant and pre-malignant human plasma cells including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and post-relapse myeloma, plasma cell leukemia, and AL amyloidosis. Consistent with human disease, NSG+hIL6 mice engrafted with patient-derived myeloma cells, developed serum M spikes, and a majority developed anemia, hypercalcemia, and/or bone lesions. Single cell RNA sequencing showed non-malignant and malignant cell engraftment, the latter expressing a wide array of mRNAs associated with myeloma cell survival and proliferation. Myeloma engrafted mice given CAR T-cells targeting plasma cells or bortezomib experienced reduced tumor burden. Our results established NSG+hIL6 mice as an effective patient derived xenograft model for study and preclinical drug development of multiple myeloma and related plasma cell disorders.