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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 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.
Fuente: Blood Advances, 2023, 7(1), 167-173
Editorial: American Society of Hematology
Fecha de publicación: 10/01/2023
Nº de páginas: 7
Tipo de publicación: Artículo de Revista
DOI: 10.1182/bloodadvances.2022008141
ISSN: 2473-9529,2473-9537
Url de la publicación: https://doi.org/10.1182/bloodadvances.2022008141
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SIMOES, CATIA
CHILLÓN, MARÍA CARMEN
MARTÍNEZ-CUADRÓN, DAVID
CALASANZ, MARÍA JOSÉ
VIDRIALES, MARÍA-BELÉN
VÁZQUEZ, IRIA
HERNÁNDEZ-RUANO, MONTSERRAT
ARICETA, BEÑAT
AGUIRRE-RUIZ, PAULA
BURGOS, LEIRE
ALIGNANI, DIEGO
VILLAR, SARA
ALFONSO, ANA
PROSPER, FELIPE
AYALA, ROSA
MARTÍNEZ-LÓPEZ, JOAQUÍN
BERGUA BURGUÉS, JUAN MIGUEL
VIVES, SUSANA
PÉREZ-SIMÓN, JOSÉ ANTONIO
MARIA DE LAS MERCEDES COLORADO ARAUJO
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