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Lookup NU author(s): Dr Luca Ermini, Dr Frederik van DelftORCiD, Dr Sarah Jenkinson, Professor Christine Harrison FRCPath FMedSci
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2018 The Author(s) Single-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.
Author(s): Furness CL, Mansur MB, Weston VJ, Ermini L, van Delft FW, Jenkinson S, Gale R, Harrison CJ, Pombo-de-Oliveira MS, Sanchez-Martin M, Ferrando AA, Kearns P, Titley I, Ford AM, Potter NE, Greaves M
Publication type: Article
Publication status: Published
Journal: Leukemia
Year: 2018
Volume: 32
Pages: 1984-1993
Online publication date: 20/03/2018
Acceptance date: 18/12/2017
Date deposited: 10/04/2018
ISSN (print): 0887-6924
ISSN (electronic): 1476-5551
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41375-018-0046-8
DOI: 10.1038/s41375-018-0046-8
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