biostudies-literatureHasanali ZSBLRD VANIAID NIH HHSNHLBI NIH HHSNCI NIH HHSe177300https://www.ebi.ac.uk/biostudies/studies/S-EPMC11141932biostudies-literatureUnknown9(10)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 sequencJCI insightHuman IL-6 fosters long-term engraftment of patient-derived disease-driving myeloma cells in immunodeficient mice.PMC11141932T32 HL007439R01 AI175185P30 CA034196I01 BX004662R01 AI139123Sheppard NCCohen ADStadtmauer EASusanibar-Adaniya SPCarroll MHasanali ZSVogl DTGarfall ALShultz LDLiu WWaxman AJDopkin DBurzenski LKadu SAllman DTang YfalseHuman IL-6 fosters long-term engraftment of patient-derived disease-driving myeloma cells in immunodeficient mice.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 sequenc2024-01-01T00:00:00Z2024 May2026-06-03T06:48:41.626Z2026-05-29T03:06:15.94ZS-EPMC111419323871351010.1172/jci.insight.177300