Publicaciones científicas

Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia

14-oct-2022 | Revista: Blood Advances

Catia Simoes  1 , Maria Carmen Chillon  2 , David Martínez-Cuadrón  3 , Maria José Calasanz  4 , María-Belén Vidriales  5 , Iria Vazquez  6 , Montserrat Hernández-Ruano  7 , Beñat Ariceta  8 , Paula Aguirre-Ruiz  9 , Leire Burgos  6 , Diego Alignani  10 , Sarai Sarvide  11 , Sara Villar  8 , Ana Alfonso  12 , Felipe Prosper  13 , Rosa Ayala  14 , Joaquin Martínez-López  15 , Juan Miguel Bergua Burgues  16 , Susana Vives  17 , Jose Antonio Perez-Simon  18 , María García-Fortes  19 , Teresa Bernal Del Castillo  20 , Mercedes Colorado  21 , Mayte Olave  22 , Juan I Rodríguez-Gutiérrez  23 , Jorge Labrador  24 , Marcos González  25 , Jesus San-Miguel  26 , Miguel A Sanz  27 , Pau Montesinos  3 , Bruno Paiva  28


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.

CITA DEL ARTÍCULO  Blood Adv. 2022 Oct 14;bloodadvances.2022008141.  doi: 10.1182/bloodadvances.2022008141