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

Autor: Potter N; The Institute of Cancer Research, London, UK., Jones L; Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK., Blair H; Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK., Strehl S; CCRI, Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria., Harrison CJ; Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK., Greaves M; The Institute of Cancer Research, London, UK., Kearney L; The Institute of Cancer Research, London, UK., Russell LJ; Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK. lisa.russell@newcastle.ac.uk.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2019 Apr; Vol. 33 (4), pp. 893-904. Date of Electronic Publication: 2018 Nov 28.
DOI: 10.1038/s41375-018-0297-4
Abstrakt: 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.
Databáze: MEDLINE
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