Portal de investigación
Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Simoes C
- Chillon MC
- Calasanz MJ
- Vridiales MB
- Vazquez I
- Hernández-Ruano M
- Ariceta B
- Aguirre-Ruiz P
- Burgos L
- Alignani D
- Sarvide S
- Villar S
- Pierola AA
- Prosper F
- Ayala R
- Martínez-López J
- Bergua Burgues JM
- Vives S
- Perez-Simon JA
- Garcia-Fortes M
- Bernal Del Castillo T
- Colorado M
- Olave M
- Rodríguez-Gutiérrez JI
- Labrador J
- González M
- San-Miguel JF
- Paiva B
Grupos
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 myelo-erythropoiesis, 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.
© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
Datos de la publicación
- ISSN/ISSNe:
- 2473-9529, 2473-9537
- Tipo:
- Article
- Páginas:
- 167-173
- PubMed:
- 36240453
- Enlace a otro recurso:
- www.scopus.com
- Factor de Impacto:
- 2,795 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Blood Advances ELSEVIER
Citas Recibidas en Web of Science: 7
Documentos
- No hay documentos
Filiaciones
Keywords
- MULTILINEAGE DYSPLASIA; MUTATIONS; AML; IMPACT
Campos de Estudio
Cita
Simoes C,Chillon MC,MARTÍNEZ D,Calasanz MJ,Vridiales MB,Vazquez I,Hernández M,Ariceta B,Aguirre P,Burgos L,Alignani D,Sarvide S,Villar S,Pierola AA,Prosper F,Ayala R,Martínez J,Bergua JM,Vives S,Perez JA,Garcia M,Bernal Del Castillo T,Colorado M,Olave M,Rodríguez JI,Labrador J,González M,San JF,SANZ MÁ,MONTESINOS P,Paiva B. Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia. Blood Adv. 2023. 7. (1):p. 167-173. IF:7,400. (1).