Document Type
Article
Publication Date
5-7-2024
Original Citation
Hasanali Z,
Garfall A,
Burzenski L,
Shultz LD,
Tang Y,
Kadu S,
Sheppard N,
Liu W,
Dopkin D,
Vogl D,
Cohen A,
Waxman A,
Susanibar-Adaniya S,
Carroll M,
Stadtmauer E,
Allman D.
Human IL-6 fosters long-term engraftment of patient-derived disease-driving myeloma cells in immunodeficient mice. JCI Insight. 2024;9(10)
Keywords
JMG, Animals, Multiple Myeloma, Humans, Mice, Interleukin-6, Disease Models, Animal, Mice, Transgenic, Bortezomib, Male, Female, Plasma Cells, Monoclonal Gammopathy of Undetermined Significance
JAX Source
JCI Insight. 2024;9(10)
ISSN
2379-3708
PMID
38713510
DOI
https://doi.org/10.1172/jci.insight.177300
Grant
CA034196 (to LDS)
Abstract
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.
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