Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice

Abstract

Most human cancers including myeloma are preceded by a precursor state. There is an unmet need for in vivo models to study the interaction of human preneoplastic cells in the bone marrow microenvironment with non-malignant cells. Here, we genetically humanized mice to permit the growth of primary human pre-neoplastic and malignant plasma cells together with non-malignant cells in vivo [?]. Growth was largely restricted to the bone marrow, mirroring the pattern in patients. Xenografts captured the genomic complexity of parental tumors and revealed additional somatic changes. Moreover, xenografts from patients with preneoplastic gammopathy showed progressive growth, suggesting that the clinical stability of these lesions may in part be due to growth controls extrinsic to tumor cells. These data demonstrate a new approach to investigate the entire spectrum of human plasma cell neoplasia and illustrate the utility of humanized models for understanding the functional diversity of human tumors [?].

Changes in bone marrow innate lymphoid cell subsets in monoclonal gammopathy: target for IMiD therapy

“…22 Therefore alteration in ILCs observed here has potential implications for immune surveillance in MM. Prospective evaluation in patients and using new humanized models 23 may help further dissect the role of ILC dysfunction in MM. Ikzf3 was previously shown to inhibit murine innate cells 24 and ikzf3 depletion has been implicated in IMiD-mediated immune activation.…”

The IL ‐6 signaling complex is a critical driver, negative prognostic factor, and therapeutic target in diffuse large B‐cell lymphoma

“…Animal experimentation, reconstitution, in vivo imaging, and tissue processing and staining M-CSF h ;IL-3/GM-CSF h ;hSIRPA tg ;TPO h ;Rag2 À ;cc À (MISTRG; Rongvaux et al, 2014) and MISTRG mice additionally expressing IL-6 h (MISTRG6; Das et al, 2016) were obtained from a local repository. For xenotransplantation studies, cell lines were injected subcutaneously (1 × 10 7 cells in 150 ll PBS) into both flanks of 6-to 8week-old mixed-gender MISTRG mice, or intravenously (1 × 10 7 cells in 100 ll PBS) into mixed-gender MISTRG or MISTRG6 mice in the orthotopic model.…”

A Hitchhiker's guide to humanized mice: new pathways to studying viral infections

“…Due to this, a further advancement of the MISTRG mouse was created, with the addition of the human Il6 by gene knock‐in, resulting in the new MISTRG‐6 strain . This new model shows improved B‐cell and malignant plasma cell development, to investigate their effects on lytic bone disease, however, this strain is yet to be used in the context of infectious disease …”

“…26 This new model shows improved B-cell and malignant plasma cell development, to investigate their effects on lytic bone disease, however, this strain is yet to be used in the context of infectious disease. 60…”