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dc.contributor.authorFurness, CL
dc.contributor.authorMansur, MB
dc.contributor.authorWeston, VJ
dc.contributor.authorErmini, L
dc.contributor.authorvan Delft, FW
dc.contributor.authorJenkinson, S
dc.contributor.authorGale, R
dc.contributor.authorHarrison, CJ
dc.contributor.authorPombo-de-Oliveira, MS
dc.contributor.authorSanchez-Martin, M
dc.contributor.authorFerrando, AA
dc.contributor.authorKearns, P
dc.contributor.authorTitley, I
dc.contributor.authorFord, AM
dc.contributor.authorPotter, NE
dc.contributor.authorGreaves, M
dc.date.accessioned2019-07-30T11:53:25Z
dc.date.issued2018-09
dc.identifier.citationLeukemia, 2018, 32 (9), pp. 1984 - 1993
dc.identifier.issn0887-6924
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3308
dc.identifier.eissn1476-5551
dc.identifier.doi10.1038/s41375-018-0046-8
dc.description.abstractSingle-cell genetics were used to interrogate clonal complexity and the sequence of mutational events in STIL-TAL1+ T-ALL. Single-cell multicolour FISH was used to demonstrate that the earliest detectable leukaemia subclone contained the STIL-TAL1 fusion and copy number loss of 9p21.3 (CDKN2A/CDKN2B locus), with other copy number alterations including loss of PTEN occurring as secondary subclonal events. In three cases, multiplex qPCR and phylogenetic analysis were used to produce branching evolutionary trees recapitulating the snapshot history of T-ALL evolution in this leukaemia subtype, which confirmed that mutations in key T-ALL drivers, including NOTCH1 and PTEN, were subclonal and reiterative in distinct subclones. Xenografting confirmed that self-renewing or propagating cells were genetically diverse. These data suggest that the STIL-TAL1 fusion is a likely founder or truncal event. Therapies targeting the TAL1 auto-regulatory complex are worthy of further investigation in T-ALL.
dc.formatPrint-Electronic
dc.format.extent1984 - 1993
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectDisease Models, Animal
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectOncogene Proteins, Fusion
dc.subjectIn Situ Hybridization, Fluorescence
dc.subjectMutation
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAlleles
dc.subjectAdolescent
dc.subjectAdult
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectPTEN Phosphohydrolase
dc.subjectPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma
dc.subjectGenome-Wide Association Study
dc.subjectYoung Adult
dc.subjectSingle-Cell Analysis
dc.subjectMultiplex Polymerase Chain Reaction
dc.subjectClonal Evolution
dc.subjectHeterografts
dc.subjectT-Cell Acute Lymphocytic Leukemia Protein 1
dc.titleThe subclonal complexity of STIL-TAL1+ T-cell acute lymphoblastic leukaemia.
dc.typeJournal Article
dcterms.dateAccepted2017-12-18
rioxxterms.versionofrecord10.1038/s41375-018-0046-8
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfLeukemia
pubs.issue9
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.publication-statusPublished
pubs.volume32
pubs.embargo.termsNo embargo
icr.researchteamBiology of Childhood Leukaemiaen_US
dc.contributor.icrauthorGreaves, Melvynen
dc.contributor.icrauthorFord, Anthonyen


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