Modelo integrado de citometría y ultrasecuenciación de nueva generación para desvelar la patogénesis de la leucemia mieloblástica aguda y definir nuevos criterios de respuesta
PI16/00517
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Nombre agencia financiadora Ministerio de Economía y Competitividad
Acrónimo agencia financiadora MINECO
Programa Programa Estatal de I+D+I Orientada a los Retos de la Sociedad
Subprograma Salud, cambio demográfico y bienestar
Convocatoria Proyectos de investigación en salud (Modalidad Proyectos de investigación en salud) (AE Salud 2016)
Año convocatoria 2016
Unidad de gestión Instituto de Salud Carlos III (ISCIII)
Centro beneficiario FUNDACIÓN INSTITUTO DE ESTUDIOS DE CIENCIAS DE LA SALUD DE CASTILLA Y LEÓN (IECSCYL)
Centro realización INSTITUTO DE INVESTIGACION BIOMEDICA DE SALAMANCA (IBSAL)
Identificador persistente http://dx.doi.org/10.13039/501100003329
Publicaciones
Resultados totales (Incluyendo duplicados): 1
Encontrada(s) 1 página(s)
Encontrada(s) 1 página(s)
Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia
Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
- Simoes, Catia
- Chillón, María Carmen
- Martínez-Cuadrón, David
- Calasanz, María José
- Vridiales, María-Belén
- Vázquez Urio, Iria
- Hernández-Ruano, Montserrat
- Ariceta, Beñat
- Aguirre-Ruiz, Paula
- Burgos, Leire
- Alignani, Diego
- Sarvide, Sarai
- Villar, Sara
- Alfonso Pierola, Ana
- Prósper, Felipe
- Ayala, Rosa
- Martínez-López, Joaquín
- Bergua Burgués, Juan Miguel
- Vives, Susana
- Pérez-Simón, José A.
- García-Fortes, María
- Bernal del Castillo, Teresa
- Colorado, Mercedes
- Olave, Mayte
- Rodríguez-Gutiérrez, Juan I.
- Labrador, Jorge
- Gonzalez Díaz, Marcos
- San-Miguel, Jesús F.
- Sanz, Miguel A.
- Montesinos, Pau
- Paiva, Bruno David Lourenço
Publicado 2023-01-10, 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., This work was supported by grants from the Área de Oncología del Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red (CIBER-ONC) (CB16/12/00369, CB16/12/00233, CB16/12/ 00489, and CB16/12/00284), Instituto de Salud Carlos III/Sub-dirección General de Investigación Sanitaria (FIS numbers PI16/ 01661, PI16/00517, and PI19/01518), and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This work was supported internationally by the Cancer Research UK, FCAECC, and AIRC under the Accelerator Award Program (EDITOR).