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Single cell analysis identifies CRLF2 rearrangements as both early and late events in Down syndrome and non-Down syndrome acute lymphoblastic leukaemia

Lookup NU author(s): Dr Helen Blair, Professor Christine Harrison, Dr Lisa Russell

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Springer Nature, 2019.

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Abstract

Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5-15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We have previously reported the genomic landscape of patients with CRLF2 rearrangements (CRLF2-r) using both whole genome and exome sequencing, which identified a number of potential clonal and sub-clonal genomic alterations. In this study, we aimed to assess when the CRLF2-r; IGH-CRLF2 or P2RY8-CRLF2, arose during the evolution of both Down syndrome-ALL (DS-ALL) and non-DS-ALL. Using fluorescence in situ hybridisation, we were able to track up to four structural variants in single cells from 47 CRLF2-r B-ALL patients, which in association with our multiplex single cell analysis of a further four patients, permitted simultaneous tracking of copy number alterations, structural and single nucleotide variants within individual cells. We observed CRLF2-r arising as both early and late events in DS and non-DS-ALL patients. Parallel evolution of discrete clones was observed in the development of CRLF2-r B-ALL, either involving the CRLF2-r or one of the other tracked abnormalities. In depth single cell analysis identified both linear and branching evolution with early clones harbouring a multitude of abnormalities, including the CRLF2-r in DS-ALL patients.


Publication metadata

Author(s): Potter N, Jones L, Blair H, Strehl S, Harrison CJ, Greaves M, Kearney L, Russell LJ

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2019

Volume: 33

Pages: 893-904

Online publication date: 28/11/2018

Acceptance date: 24/09/2018

Date deposited: 27/09/2018

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Springer Nature

URL: https://doi.org/10.1038/s41375-018-0297-4

DOI: 10.1038/s41375-018-0297-4


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