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dc.contributor.authorPotter, Nen_US
dc.contributor.authorMiraki-Moud, Fen_US
dc.contributor.authorErmini, Len_US
dc.contributor.authorTitley, Ien_US
dc.contributor.authorVijayaraghavan, Gen_US
dc.contributor.authorPapaemmanuil, Een_US
dc.contributor.authorCampbell, Pen_US
dc.contributor.authorGribben, Jen_US
dc.contributor.authorTaussig, Den_US
dc.contributor.authorGreaves, Men_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2018-11-19T11:55:03Z
dc.date.issued2019-05en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30568172en_US
dc.identifier10.1038/s41375-018-0319-2en_US
dc.identifier.citationLeukemia, 2019, 33 (5), pp. 1113 - 1123en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2939
dc.identifier.eissn1476-5551en_US
dc.identifier.doi10.1038/s41375-018-0319-2en_US
dc.description.abstractWe used single cell Q-PCR on a micro-fluidic platform (Fluidigm) to analyse clonal, genetic architecture and phylogeny in acute myeloid leukaemia (AML) using selected mutations. Ten cases of NPM1c mutant AML were screened for 111 mutations that are recurrent in AML and cancer. Clonal architectures were relatively simple with one to six sub-clones and were branching in some, but not all, patients. NPM1 mutations were secondary or sub-clonal to other driver mutations (DNM3TA, TET2, WT1 and IDH2) in all cases. In three of the ten cases, single cell analysis of enriched CD34+/CD33- cells revealed a putative pre-leukaemic sub-clone, undetectable in the bulk CD33+ population that had one or more driver mutations but lacked NPM1c. Cells from all cases were transplanted into NSG mice and in most (8/10), more than one sub-clone (#2-5 sub-clones) transplanted. However, the dominant regenerating sub-clone in 9/10 cases was NPM1+ and this sub-clone was either dominant or minor in the diagnostic sample from which it was derived. This study provides further evidence, at the single cell level, for genetic variegation in sub-clones and stem cells in acute leukaemia and demonstrates both a preferential order of mutation accrual and parallel evolution of sub-clones.en_US
dc.format.extent1113 - 1123en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleSingle cell analysis of clonal architecture in acute myeloid leukaemia.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-11-06en_US
rioxxterms.versionofrecord10.1038/s41375-018-0319-2en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2019-05en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfLeukemiaen_US
pubs.issue5en_US
pubs.notesNot knownen_US
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/Acute Leukaemia
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.publication-statusPublisheden_US
pubs.volume33en_US
pubs.embargo.termsNot knownen_US
icr.researchteamAcute Leukaemiaen_US
icr.researchteamBiology of Childhood Leukaemiaen_US
dc.contributor.icrauthorGreaves, Melvynen_US
dc.contributor.icrauthorMiraki-Moud, Faridehen_US


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