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

First Author  Das R Year  2016
Journal  Nat Med Volume  22
Issue  11 Pages  1351-1357
PubMed ID  27723723 Mgi Jnum  J:240722
Mgi Id  MGI:5888974 Doi  10.1038/nm.4202
Citation  Das R, et al. (2016) Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice. Nat Med 22(11):1351-1357
abstractText  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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