Human IL-6 fosters long-term engraftment of patient-derived disease-driving myeloma cells in immunodeficient mice.
JCI Insight
; 9(10)2024 May 07.
Article
em En
| MEDLINE
| ID: mdl-38713510
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-6
/
Mieloma Múltiplo
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article