| Autor: |
Hasanali ZS, Garfall AL, Burzenski L, Shultz LD, Tang Y, Kadu S, Sheppard NC, Dopkin D, Vogl DT, Cohen AD, Waxman AJ, Susanibar-Adaniya SP, Carroll M, Stadtmauer EA, Allman D |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 24. Date of Electronic Publication: 2024 Jan 24. |
| DOI: |
10.1101/2024.01.21.576547 |
| Abstrakt: |
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 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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