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Microenvironment-dependent growth of pre-neoplastic and malignant plasma cells in humanized mice
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 hu...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101153/ https://www.ncbi.nlm.nih.gov/pubmed/27723723 http://dx.doi.org/10.1038/nm.4202 |
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author | Das, Rituparna Strowig, Till Verma, Rakesh Koduru, Srinivas Hafemann, Anja Hopf, Stephanie Kocoglu, Mehmet H. Borsotti, Chiara Zhang, Lin Branagan, Andrew Eynon, Elizabeth Manz, Markus G. Flavell, Richard A. Dhodapkar, Madhav V. |
author_facet | Das, Rituparna Strowig, Till Verma, Rakesh Koduru, Srinivas Hafemann, Anja Hopf, Stephanie Kocoglu, Mehmet H. Borsotti, Chiara Zhang, Lin Branagan, Andrew Eynon, Elizabeth Manz, Markus G. Flavell, Richard A. Dhodapkar, Madhav V. |
author_sort | Das, Rituparna |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5101153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-51011532017-04-10 Microenvironment-dependent growth of pre-neoplastic and malignant plasma cells in humanized mice Das, Rituparna Strowig, Till Verma, Rakesh Koduru, Srinivas Hafemann, Anja Hopf, Stephanie Kocoglu, Mehmet H. Borsotti, Chiara Zhang, Lin Branagan, Andrew Eynon, Elizabeth Manz, Markus G. Flavell, Richard A. Dhodapkar, Madhav V. Nat Med Article 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. 2016-10-10 2016-11 /pmc/articles/PMC5101153/ /pubmed/27723723 http://dx.doi.org/10.1038/nm.4202 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Das, Rituparna Strowig, Till Verma, Rakesh Koduru, Srinivas Hafemann, Anja Hopf, Stephanie Kocoglu, Mehmet H. Borsotti, Chiara Zhang, Lin Branagan, Andrew Eynon, Elizabeth Manz, Markus G. Flavell, Richard A. Dhodapkar, Madhav V. Microenvironment-dependent growth of pre-neoplastic and malignant plasma cells in humanized mice |
title | Microenvironment-dependent growth of pre-neoplastic and malignant
plasma cells in humanized mice |
title_full | Microenvironment-dependent growth of pre-neoplastic and malignant
plasma cells in humanized mice |
title_fullStr | Microenvironment-dependent growth of pre-neoplastic and malignant
plasma cells in humanized mice |
title_full_unstemmed | Microenvironment-dependent growth of pre-neoplastic and malignant
plasma cells in humanized mice |
title_short | Microenvironment-dependent growth of pre-neoplastic and malignant
plasma cells in humanized mice |
title_sort | microenvironment-dependent growth of pre-neoplastic and malignant
plasma cells in humanized mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101153/ https://www.ncbi.nlm.nih.gov/pubmed/27723723 http://dx.doi.org/10.1038/nm.4202 |
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