A miRNA signature related to stemness identifies high-risk patients in paediatric acute myeloid leukaemia
Por:
Esperanza-Cebollada E, Gomez-Gonzalez S, Pérez-Jaume S, Vega-García N, Vicente-Garces C, Richarte M, Rives-Solà S, Català-Temprano A, Torrebadell-Burriel M and Camós-Guijosa M
Publicada:
1 jul 2023
Ahead of Print:
1 mar 2023
Categoría:
Hematology
Resumen:
Clinical and biological variables like genetic aberrations at diagnosis and the levels of measurable residual disease (MRD) are the most powerful biomarkers to predict the outcome of paediatric leukaemia. Recently, a model integrating the genetic abnormalities, transcriptional identity, and leukaemia stemness measured as leukaemic stem cell score (pLSC6) has been proposed to identify high-risk paediatric acute myeloid leukaemia (AML) patients. However, the role of epigenetics in defining prognosis still needs to be established. We evaluated the role of 89 miRNAs regulating stemness and their contribution to predicting outcomes in 110 paediatric patients with acute leukaemia. We identified a 24-miRNA signature capable of distinguishing paediatric AML patients with excellent or poor outcomes. We validated these results in an independent cohort using public repository-based data. The 24-miRNA signature was significantly associated with the leukaemic stemness scores and the underlying genetics of patients. Notably, the combination of classical prognostic factors (MRD and genetics), the pLSC6 score and the 24-miRNA signature had a higher capacity to predict the overall and event-free survival than each variable individually. Our 24-miRNA signature provides epigenetic data to integrate into genetics, MRD and stemness-related leukaemic scores to refine risk stratification in paediatric AML patients.
Filiaciones:
Esperanza-Cebollada E:
Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain
Gomez-Gonzalez S:
Developmental Tumors Biology Group, Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain
Pérez-Jaume S:
Developmental Tumors Biology Group, Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain
Vega-García N:
Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain
Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Vicente-Garces C:
Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain
Richarte M:
Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain
Rives-Solà S:
Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain
Pediatric Hematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Català-Temprano A:
Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain
Pediatric Hematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Torrebadell-Burriel M:
Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain
Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Camós-Guijosa M:
Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Hospital Sant Joan de Déu, Barcelona, Spain
Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
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