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A new humanized mouse model has been developed by a team of researchers at Yale University, in order to study Multiple Myeloma (MM) in-vivo. Rituparna Das, along with Professors Richard A. Flavell and Madhav V. Dhodapkar, published their findings in Nature Medicine in November 2016. Notably, this model enables growth of pre-neoplastic plasma cells as well as malignant cells, and therefore also allows study of the precursor disease state of monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic MM (AMM). The authors found that both xenografts from patients with MM or cells from the precursor state were supported in this mouse model, signifying a strong role for extrinsic cues from the microenvironment.
In conclusion, the advantage of MIS(KI)TRG6 mice over other MM models is the ability to support growth of primary tumor cells, in both pre-neoplastic and more advanced malignant states, in-vivo. In addition, growth of tumor cells is largely restricted to the bone marrow, which is consistent with human MM. Ultimately, this mouse model will enable detailed studies of MM biology and development from early precursor states, as well as pre-clinical testing and the development of personalized therapies.
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 preneoplastic and malignant plasma cells together with non-malignant cells in vivo. Growth was largely restricted to the bone marrow, mirroring the pattern in patients with myeloma. 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.
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