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Human IL-6 fosters long-term engraftment of human patient derived myeloma cells in immunodeficient mice

ABSTRACT: Human IL-6 fosters long-term engraftment of human patient derived myeloma cells in immunodeficient mice

PROVIDER: PRJNA1031637 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26500103_1.fastq.gz	Fastqsanger.gz
	SRR26500103_2.fastq.gz	Fastqsanger.gz
	SRR26500104_1.fastq.gz	Fastqsanger.gz
	SRR26500104_2.fastq.gz	Fastqsanger.gz

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Human IL-6 fosters long-term engraftment of human patient derived myeloma cells in immunodeficient mice

Project description: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 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 blood M spikes, and a majority developed anemia, hypercalcemia, and/or bone lesions. Singe cell RNAseq analyses 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 that NSG+hIL6 mice provide an effective patient derived xenograft model for study and preclinincal drug development for myeloma and related plasma cell disorders.

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PDGFB-expressing MSCs improve human hematopoietic stem cell engraftment in immunodeficient mice

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