Header

UZH-Logo

Maintenance Infos

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


Das, R; Srowig, T; Verma, R; Koduru, S; Hafemann, A; Hopf, S; Kocoglu, M H; Borsotti, C; Zhang, L; Branagan, A; Eynon, E; Manz, M G; Flavell, R A; Dhodapkar, M V (2016). Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice. Nature Medicine, 22(11):1351-1357.

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.

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.

Statistics

Citations

3 citations in Web of Science®
3 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 07 Feb 2017
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:November 2016
Deposited On:07 Feb 2017 13:50
Last Modified:07 Feb 2017 13:50
Publisher:Nature Publishing Group
ISSN:1078-8956
Publisher DOI:https://doi.org/10.1038/nm.4202
PubMed ID:27723723

Download

Preview Icon on Download
Content: Published Version
Filetype: PDF - Registered users only
Size: 2MB
View at publisher