dc.creator | Simoes, Catia | es |
dc.creator | Chillón, María Carmen | es |
dc.creator | Martínez-Cuadrón, David | es |
dc.creator | Calasanz, María José | es |
dc.creator | Vridiales, María Belén | es |
dc.creator | Vazquez, Iria | es |
dc.creator | Ruano, Montserrat | es |
dc.creator | Pérez Simón, José Antonio | es |
dc.creator | Paiva, Bruno | es |
dc.date.accessioned | 2024-05-02T14:53:58Z | |
dc.date.available | 2024-05-02T14:53:58Z | |
dc.date.issued | 2023-01-10 | |
dc.identifier.citation | Simoes, C., Chillón, M.C., Martínez-Cuadrón, D., Calasanz, M.J., Vridiales, M.B., Vazquez, I.,...,Paiva, B. (2023). Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia. Blood Advances, 7 (1), 167-173. https://doi.org/10.1182/bloodadvances.2022008141. | |
dc.identifier.issn | 2473-9529 | es |
dc.identifier.uri | https://hdl.handle.net/11441/157472 | |
dc.description.abstract | Clonal evolution in acute myeloid leukemia (AML) originates long before diagnosis and is a
dynamic process that may affect survival. However, it remains uninvestigated during
routine diagnostic workups. We hypothesized that the mutational status of bone marrow
dysplastic cells and leukemic blasts, analyzed at the onset of AML using integrated
multidimensional flow cytometry (MFC) immunophenotyping and fluorescence-activated
cell sorting (FACS) with next-generation sequencing (NGS), could reconstruct
leukemogenesis. Dysplastic cells were detected by MFC in 285 of 348 (82%) newly diagnosed
patients with AML. Presence of dysplasia according to MFC and World Health Organization
criteria had no prognostic value in older adults. NGS of dysplastic cells and blasts isolated at
diagnosis identified 3 evolutionary patterns: stable (n = 12 of 21), branching (n = 4 of 21),
and clonal evolution (n = 5 of 21). In patients achieving complete response (CR), integrated
MFC and FACS with NGS showed persistent measurable residual disease (MRD) in
phenotypically normal cell types, as well as the acquisition of genetic traits associated with
treatment resistance. Furthermore, whole-exome sequencing of dysplastic and leukemic
cells at diagnosis and of MRD uncovered different clonal involvement in dysplastic myeloerythropoiesis, leukemic transformation, and chemoresistance. Altogether, we showed that
it is possible to reconstruct leukemogenesis in ~80% of patients with newly diagnosed AML,
using techniques other than single-cell multiomics. | es |
dc.format | application/pdf | es |
dc.format.extent | 7 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | Blood Advances, 7 (1), 167-173. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.publisherversion | https://ashpublications.org/bloodadvances/article/7/1/167/486809/Integrated-flow-cytometry-and-sequencing-to | es |
dc.identifier.doi | 10.1182/bloodadvances.2022008141 | es |
dc.journaltitle | Blood Advances | es |
dc.publication.volumen | 7 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 167 | es |
dc.publication.endPage | 173 | es |