| First Author | Hasanali ZS | Year | 2024 |
| Journal | JCI Insight | Volume | 9 |
| Issue | 10 | PubMed ID | 38713510 |
| Mgi Jnum | J:348801 | Mgi Id | MGI:7645442 |
| Doi | 10.1172/jci.insight.177300 | Citation | Hasanali ZS, et al. (2024) Human IL-6 fosters long-term engraftment of patient-derived disease-driving myeloma cells in immunodeficient mice. JCI Insight 9(10) |
| abstractText | 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 human IL-6-transgenic (hIL-6-transgenic) NSG (NSG+hIL6) mice reliably support the engraftment of malignant and premalignant human plasma cells, including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and postrelapse myeloma, plasma cell leukemia, and amyloid light chain 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 nonmalignant 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 establish NSG+hIL6 mice as an effective patient-derived xenograft model for study and preclinical drug development of multiple myeloma and related plasma cell disorders. |
