Single-cell analysis identifies CRLF2 rearrangements as both early and late events in Down syndrome and non-Down syndrome acute lymphoblastic leukaemia.
Adolescent
Adult
Animals
Case-Control Studies
Child
Child, Preschool
Down Syndrome
/ complications
Female
Gene Rearrangement
Humans
In Situ Hybridization, Fluorescence
Infant
Leukemia, Myeloid, Acute
/ complications
Male
Mice, Inbred NOD
Mice, SCID
Middle Aged
Mutation
Receptors, Cytokine
/ genetics
Single-Cell Analysis
/ methods
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Young Adult
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
10
07
2018
accepted:
24
09
2018
revised:
19
09
2018
pubmed:
30
11
2018
medline:
10
8
2019
entrez:
30
11
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30487598
doi: 10.1038/s41375-018-0297-4
pii: 10.1038/s41375-018-0297-4
pmc: PMC6398588
mid: EMS79778
doi:
Substances chimiques
CRLF2 protein, human
0
Receptors, Cytokine
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
893-904Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 105104/Z/14/Z
Pays : United Kingdom
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