Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia
| Autor: | Catia Simoes, Maria-Carmen Chillon, David Martínez-Cuadrón, Maria-José Calasanz, María-Belén Vridiales, Iria Vazquez, Montserrat Hernández-Ruano, Beñat Ariceta, Paula Aguirre-Ruiz, Leire Burgos, Diego Alignani, Sarai Sarvide, Sara Villar, Ana Alfonso Pierola, Felipe Prosper, Rosa Ayala, Joaquin Martínez-López, Juan Miguel Bergua Burgues, Susana Vives, Jose A. Perez-Simon, Maria Garcia-Fortes, Teresa Bernal del Castillo, Mercedes Colorado, Mayte Olave, Juan I. Rodríguez-Gutiérrez, Jorge Labrador, Marcos González, Jesús F. San-Miguel, Miguel Ángel Sanz, Pau Montesinos, Bruno Paiva |
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| Přispěvatelé: | Universidad de Cantabria |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Blood Advances r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe instname Blood advances, 2023, 7(1), 167-173 |
| ISSN: | 2473-9529 |
| Popis: | 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 workup. 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 sorting (FACS) with next-generation sequencing (NGS), could reconstruct leukemogenesis. Dysplastic cells were detected by MFC in 285 of 348 (82%) newly-diagnosed AML patients. Presence of dysplasia according to MFC and WHO criteria had no prognostic value in the elderly. NGS of dysplastic cells and blasts isolated at diagnosis identified three evolutionary patterns: stable (n=12/21), branching (n=4/21) and clonal evolution (n=5/21). In patients achieving complete response, 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 approximately 80% of newly diagnosed AML patients, using techniques other than single-cell multiomics. ACKNOWLEDGEMENTS: The authors acknowledge the patients, caregivers, and the biobank of the University of Navarra. This work was supported by grants from the Área de Oncología del Instituto de Salud Carlos III, Centro de Investigacion Biom ´ edica en ´ Red (CIBER-ONC) (CB16/12/00369, CB16/12/00233, CB16/12/ 00489, and CB16/12/00284), Instituto de Salud Carlos III/Subdireccion General de Investigaci ´ on Sanitaria (FIS numbers PI16/ ´ 01661, PI16/00517, and PI19/01518), and the Plan de Investigacion´ 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). |
| Databáze: | OpenAIRE |
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