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

Rituparna Das, Till Strowig, Rakesh Verma, Srinivas Koduru, Anja Hafemann, Stephanie Hopf, Mehmet H. Kocoglu, Chiara Borsotti, Lin Zhang, Andrew Branagan, Elizabeth Eynon, Markus G. Manz, Richard A. Flavell, Madhav V. Dhodapkar

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1351-1357
Number of pages7
JournalNature Medicine
Volume22
Issue number11
DOIs
StatePublished - Nov 1 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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