{"doi":"10.1101/2024.01.21.576547","title":"Human IL-6 fosters long-term engraftment of patient derived disease-driving myeloma cells in immunodeficient mice","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 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":489762,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":615861,"name":"Alfred L. Garfall","orcid":"0000-0003-2791-5748","position":1,"is_corresponding":false},{"id":535741,"name":"Lisa Burzenski","orcid":null,"position":2,"is_corresponding":false},{"id":239998,"name":"Leonard D. Shultz","orcid":"0000-0002-4868-1031","position":3,"is_corresponding":false},{"id":1050638,"name":"Yan Tang","orcid":"0000-0002-8655-2222","position":4,"is_corresponding":false},{"id":344178,"name":"Siddhant Kadu","orcid":"0009-0000-3616-5243","position":5,"is_corresponding":false},{"id":618835,"name":"Neil C. Sheppard","orcid":"0000-0002-9551-9491","position":6,"is_corresponding":false},{"id":870655,"name":"Derek Dopkin","orcid":null,"position":7,"is_corresponding":false},{"id":550342,"name":"Dan T. Vogl","orcid":"0000-0002-2935-2566","position":8,"is_corresponding":false},{"id":526856,"name":"Adam D. Cohen","orcid":"0000-0003-0939-3843","position":9,"is_corresponding":false},{"id":760000,"name":"Adam Waxman","orcid":"0000-0001-5217-1221","position":10,"is_corresponding":false},{"id":1186464,"name":"Sandra P. Susanibar-Adaniya","orcid":"0000-0003-0703-2518","position":11,"is_corresponding":false},{"id":318325,"name":"Martin Carroll","orcid":"0000-0002-5622-3735","position":12,"is_corresponding":false},{"id":459220,"name":"Edward A. Stadtmauer","orcid":"0000-0002-3935-6069","position":13,"is_corresponding":false},{"id":230388,"name":"David Allman","orcid":"0000-0001-9345-1502","position":14,"is_corresponding":false},{"id":975761,"name":"Zainul S. Hasanali","orcid":"0000-0002-9150-089X","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:08:28.548530Z","pmid":"38328086","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}