PersonALL: a genetic scoring guide for personalized risk assessment in pediatric B-cell precursor acute lymphoblastic leukemia.

Autor: Bedics G; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Egyed B; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Kotmayer L; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Benard-Slagter A; MRC Holland, Amsterdam, The Netherlands., de Groot K; MRC Holland, Amsterdam, The Netherlands., Bekő A; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Hegyi LL; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Bátai B; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Krizsán S; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Kriván G; Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary., Erdélyi DJ; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Müller J; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Haltrich I; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Kajtár B; Department of Pathology, University of Pécs Medical School, Pécs, Hungary., Pajor L; Department of Pathology, University of Pécs Medical School, Pécs, Hungary., Vojcek Á; Department of Pediatrics, University of Pécs Medical School, Pécs, Hungary., Ottóffy G; Department of Pediatrics, University of Pécs Medical School, Pécs, Hungary., Ujfalusi A; Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Szegedi I; Division of Pediatric Hematology-Oncology, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Tiszlavicz LG; Department of Paediatrics and Paediatric Health Care Center, Faculty of Medicine, University of Szeged, Szeged, Hungary., Bartyik K; Department of Paediatrics and Paediatric Health Care Center, Faculty of Medicine, University of Szeged, Szeged, Hungary., Csanádi K; Hemato-Oncology Unit, Heim Pál Children's Hospital, Budapest, Hungary., Péter G; Hemato-Oncology Unit, Heim Pál Children's Hospital, Budapest, Hungary., Simon R; Hemato-Oncology and Stem Cell Transplantation Unit, Velkey László Children's Health Center, Miskolc, Hungary., Hauser P; Hemato-Oncology and Stem Cell Transplantation Unit, Velkey László Children's Health Center, Miskolc, Hungary., Kelemen Á; Hemato-Oncology and Stem Cell Transplantation Unit, Velkey László Children's Health Center, Miskolc, Hungary., Sebestyén E; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Jakab Z; Hungarian Childhood Cancer Registry, Hungarian Pediatric Oncology Network, Budapest, Hungary., Matolcsy A; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.; Department of Laboratory Medicine, Karolinska Institute, Solna, Sweden., Kiss C; Division of Pediatric Hematology-Oncology, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Kovács G; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Savola S; MRC Holland, Amsterdam, The Netherlands., Bödör C; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Alpár D; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. alpar.donat@med.semmelweis-univ.hu.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2023 Aug; Vol. 129 (3), pp. 455-465. Date of Electronic Publication: 2023 Jun 21.
DOI: 10.1038/s41416-023-02309-8
Abstrakt: Background: Recurrent genetic lesions provide basis for risk assessment in pediatric acute lymphoblastic leukemia (ALL). However, current prognostic classifiers rely on a limited number of predefined sets of alterations.
Methods: Disease-relevant copy number aberrations (CNAs) were screened genome-wide in 260 children with B-cell precursor ALL. Results were integrated with cytogenetic data to improve risk assessment.
Results: CNAs were detected in 93.8% (n = 244) of the patients. First, cytogenetic profiles were combined with IKZF1 status (IKZF1 normal , IKZF1 del and IKZF1 plus ) and three prognostic subgroups were distinguished with significantly different 5-year event-free survival (EFS) rates, IKAROS-low (n = 215): 86.3%, IKAROS-medium (n = 27): 57.4% and IKAROS-high (n = 18): 37.5%. Second, contribution of genetic aberrations to the clinical outcome was assessed and an aberration-specific score was assigned to each prognostically relevant alteration. By aggregating the scores of aberrations emerging in individual patients, personalized cumulative values were calculated and used for defining four prognostic subgroups with distinct clinical outcomes. Two favorable subgroups included 60% of patients (n = 157) with a 5-year EFS of 96.3% (excellent risk, n = 105) and 87.2% (good risk, n = 52), respectively; while 40% of patients (n = 103) showed high (n = 74) or ultra-poor (n = 29) risk profile (5-year EFS: 67.4% and 39.0%, respectively).
Conclusions: PersonALL, our conceptually novel prognostic classifier considers all combinations of co-segregating genetic alterations, providing a highly personalized patient stratification.
(© 2023. The Author(s).)
Databáze: MEDLINE
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