A non-canonical lymphoblast in refractory childhood T-cell leukaemia
Abstract
Abstract 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.
Article Details
Authors (29)
Bram S. J. Lim
Holly J. Whitfield
Mi K. Trinh
Gianna Bloye
Rebecca Thomas
Great Ormond Street Hospital for Children NHS Trust, London
Nathaniel D. Anderson
Anna Wenger
Angus Hodder
Taryn D. Treger
Henry Lee-Six
Tim H. H. Coorens
Conor Parks
Toochi Ogbonnah
Petri Pölönen
Charles G. Mullighan
David T. Teachey
Jason Xu
Kai Tan
Melanie Hagleitner
Lennart Kester
Frank N. van Leeuwen
Gordon Beattie
Marc R. Mansour
Owen Williams
Jack Bartram
Stuart Adams
Great Ormond Street Hospital for Children NHS Trust, London
Laura Jardine
Sam Behjati
David O’Connor
Great Ormond Street Hospital for Children NHS Trust, London