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The subclonal complexity of STIL-TAL1+ T-cell acute lymphoblastic leukaemia

Lookup NU author(s): Dr Luca Ermini, Dr Frederik van Delft, Dr Sarah Jenkinson, Professor Christine Harrison FRCPath FMedSci

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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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