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A non-canonical lymphoblast in refractory childhood T-cell leukaemia

Title: A non-canonical lymphoblast in refractory childhood T-cell leukaemia
Authors: Lim BSJ; Whitfield HJ; Trinh MK; Bloye G; Thomas R; Anderson ND; Wenger A; Hodder A; Treger TD; Lee-Six H; Coorens THH; Parks C; Ogbonnah T; Polonen P; Mullighan CG; Teachey DT; Xu J; Tan K; Hagleitner M; Kester L; van Leeuwen FN; Beattie G; Mansour MR; Williams O; Bartram J; Adams S; Jardine L; Behjati S; O'Connor D
Source: Nature Communications, December 2025
Publisher Information: Springer Nature
Publication Year: 2025
Collection: Newcastle University Library ePrints Service
Description: © The Author(s) 2025. Refractory cancers may arise either through the acquisition of resistance mechanisms or represent distinct disease states. The origin of childhood T-cell acute lymphoblastic leukaemia (T-ALL) that does not respond to initial treatment, i.e. refractory disease, is unknown. Refractory T-ALL carries a poor prognosis and cannot be predicted at diagnosis. Here, we perform single cell mRNA sequencing of T-ALL from 58 children (84 samples) who did, or did not respond to initial treatment. We identify a transcriptionally distinctive blast population, exhibiting features of innate-like lymphocytes, as the major source of refractory disease. Evidence of such blasts at diagnosis heralds refractory disease across independent datasets and is associated with survival in a large, contemporary trial cohort. Our findings portray refractory T-ALL as a distinct disease with the potential for immediate clinical utility.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
Relation: https://eprints.ncl.ac.uk/308933; https://eprints.ncl.ac.uk/fulltext.aspx?url=308933/DB681594-5FCB-4118-8658-8CDC458BE858.pdf&pub_id=308933
Availability: https://eprints.ncl.ac.uk/308933
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.EA672CD9
Database: BASE