Genetic modification of primary human B cells to model high-grade lymphoma

Rebecca Caeser, Miriam Di Re, Joanna A. Krupka, Jie Gao, Maribel Lara-Chica, João M. L. Dias, Susanna L. Cooke, Rachel Fenner, Zelvera Usheva, Hendrik F. P. Runge, Philip A. Beer, Hesham Eldaly, Hyo-Kyung Pak, Chan-Sik Park, George S. Vassiliou, Brian J. P. Huntly, Annalisa Mupo, Rachael J. M. Bashford-Rogers and Daniel J. Hodson ()
Additional contact information
Rebecca Caeser: Wellcome MRC Cambridge Stem Cell Institute
Miriam Di Re: Wellcome MRC Cambridge Stem Cell Institute
Joanna A. Krupka: Wellcome MRC Cambridge Stem Cell Institute
Jie Gao: Wellcome MRC Cambridge Stem Cell Institute
Maribel Lara-Chica: University of Cambridge
João M. L. Dias: University of Cambridge
Susanna L. Cooke: University of Glasgow
Rachel Fenner: Wellcome MRC Cambridge Stem Cell Institute
Zelvera Usheva: Wellcome MRC Cambridge Stem Cell Institute
Hendrik F. P. Runge: Wellcome MRC Cambridge Stem Cell Institute
Philip A. Beer: Wellcome Genome Campus
Hesham Eldaly: Cambridge University Hospitals
Hyo-Kyung Pak: Asan Medical Centre
Chan-Sik Park: Asan Medical Centre
George S. Vassiliou: Wellcome MRC Cambridge Stem Cell Institute
Brian J. P. Huntly: Wellcome MRC Cambridge Stem Cell Institute
Annalisa Mupo: University of Cambridge
Rachael J. M. Bashford-Rogers: Wellcome Centre for Human Genetics
Daniel J. Hodson: Wellcome MRC Cambridge Stem Cell Institute

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract Sequencing studies of diffuse large B cell lymphoma (DLBCL) have identified hundreds of recurrently altered genes. However, it remains largely unknown whether and how these mutations may contribute to lymphomagenesis, either individually or in combination. Existing strategies to address this problem predominantly utilize cell lines, which are limited by their initial characteristics and subsequent adaptions to prolonged in vitro culture. Here, we describe a co-culture system that enables the ex vivo expansion and viral transduction of primary human germinal center B cells. Incorporation of CRISPR/Cas9 technology enables high-throughput functional interrogation of genes recurrently mutated in DLBCL. Using a backbone of BCL2 with either BCL6 or MYC, we identify co-operating genetic alterations that promote growth or even full transformation into synthetically engineered DLBCL models. The resulting tumors can be expanded and sequentially transplanted in vivo, providing a scalable platform to test putative cancer genes and to create mutation-directed, bespoke lymphoma models.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-12494-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12494-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-12494-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().