dc.contributor.author | Turati, VA | |
dc.contributor.author | Guerra-Assunção, JA | |
dc.contributor.author | Potter, NE | |
dc.contributor.author | Gupta, R | |
dc.contributor.author | Ecker, S | |
dc.contributor.author | Daneviciute, A | |
dc.contributor.author | Tarabichi, M | |
dc.contributor.author | Webster, AP | |
dc.contributor.author | Ding, C | |
dc.contributor.author | May, G | |
dc.contributor.author | James, C | |
dc.contributor.author | Brown, J | |
dc.contributor.author | Conde, L | |
dc.contributor.author | Russell, LJ | |
dc.contributor.author | Ancliff, P | |
dc.contributor.author | Inglott, S | |
dc.contributor.author | Cazzaniga, G | |
dc.contributor.author | Biondi, A | |
dc.contributor.author | Hall, GW | |
dc.contributor.author | Lynch, M | |
dc.contributor.author | Hubank, M | |
dc.contributor.author | Macaulay, I | |
dc.contributor.author | Beck, S | |
dc.contributor.author | Van Loo, P | |
dc.contributor.author | Jacobsen, SE | |
dc.contributor.author | Greaves, M | |
dc.contributor.author | Herrero, J | |
dc.contributor.author | Enver, T | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-08-23T09:33:50Z | |
dc.date.available | 2022-08-23T09:33:50Z | |
dc.date.issued | 2021-07-05 | |
dc.identifier.citation | Nature Cancer, 2021, 2 (8), pp. 835 - 852 | |
dc.identifier.issn | 2662-1347 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5300 | |
dc.identifier.eissn | 2662-1347 | |
dc.identifier.eissn | 2662-1347 | |
dc.identifier.doi | 10.1038/s43018-021-00219-3 | |
dc.description.abstract | Comparison of intratumor genetic heterogeneity in cancer at diagnosis and relapse suggests that chemotherapy induces bottleneck selection of subclonal genotypes. However, evolutionary events subsequent to chemotherapy could also explain changes in clonal dominance seen at relapse. We, therefore, investigated the mechanisms of selection in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) during induction chemotherapy where maximal cytoreduction occurs. To distinguish stochastic versus deterministic events, individual leukemias were transplanted into multiple xenografts and chemotherapy administered. Analyses of the immediate post-treatment leukemic residuum at single-cell resolution revealed that chemotherapy has little impact on genetic heterogeneity. Rather, it acts on extensive, previously unappreciated, transcriptional and epigenetic heterogeneity in BCP-ALL, dramatically reducing the spectrum of cell states represented, leaving a genetically polyclonal but phenotypically uniform population with hallmark signatures relating to developmental stage, cell cycle and metabolism. Hence, canalization of cell state accounts for a significant component of bottleneck selection during induction chemotherapy. | |
dc.format | Print-Electronic | |
dc.format.extent | 835 - 852 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation.ispartof | Nature Cancer | |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Burkitt Lymphoma | |
dc.subject | Cell Cycle | |
dc.subject | Humans | |
dc.subject | Induction Chemotherapy | |
dc.subject | Precursor Cell Lymphoblastic Leukemia-Lymphoma | |
dc.subject | Recurrence | |
dc.title | Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-05-11 | |
dc.date.updated | 2022-08-23T09:26:25Z | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1038/s43018-021-00219-3 | |
rioxxterms.licenseref.startdate | 2021-07-05 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/34734190 | |
pubs.issue | 8 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.) | |
pubs.publication-status | Published | |
pubs.volume | 2 | |
icr.researchteam | Evol Genomics & Modelling | |
icr.researchteam | Biol Childhood Leukaemia | |
dc.contributor.icrauthor | James, Chela | |
dc.contributor.icrauthor | Greaves, Melvyn | |
icr.provenance | Deposited by Dr Chela James on 2022-08-23. Deposit type is initial. No. of files: 1. Files: Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia.pdf | |