| Title: |
A non-canonical lymphoblast in refractory childhood T-cell leukaemia |
| Authors: |
Lim, Bram SJ; Whitfield, Holly J; Trinh, Mi K; Bloye, Gianna; Thomas, Rebecca; Anderson, Nathaniel D; Wenger, Anna; Hodder, Angus; Treger, Taryn D; Lee-Six, Henry; Coorens, Tim HH; Parks, Conor; Ogbonnah, Toochi; Polonen, Petri; Mullighan, Charles G; Teachey, David T; Xu, Jason; Tan, Kai; Hagleitner, Melanie; Kester, Lennart; van Leeuwen, Frank N; Beattie, Gordon; Mansour, Marc R; Williams, Owen; Bartram, Jack; Adams, Stuart; Jardine, Laura; Behjati, Sam; O'connor, David |
| Source: |
Nature Communications , 16 (1) , Article 9397. (2025) |
| Publisher Information: |
NATURE PORTFOLIO |
| Publication Year: |
2025 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Acute lymphocytic leukaemia; Cancer genomics; Cancer therapy |
| Description: |
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: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10219660/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10219660/1/A%20non-canonical%20lymphoblast%20in%20refractory%20childhood%20T-cell%20leukaemia.pdf; https://discovery.ucl.ac.uk/id/eprint/10219660/ |
| Rights: |
open |
| Accession Number: |
edsbas.1AAABAE |
| Database: |
BASE |