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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 FRCPath FMedSci, Dr Lisa Russell



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

For re-use rights please refer to the publisher's terms and conditions.


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


DOI: 10.1038/s41375-018-0297-4


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Funder referenceFunder name
15036Bloodwise (Formerly Leukaemia and Lymphoma Research) Closed Competition