Next-Generation Sequencing-Based Genomic Profiling of Children with Acute Myeloid Leukemia.

Autor:	Krizsán S; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Péterffy B; 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., Nagy T; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary; Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Sebestyén E; 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., Jakab Z; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Erdélyi DJ; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Müller J; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Péter G; Hemato-Oncology Unit, Heim Pal Children's Hospital, Budapest, Hungary., Csanádi K; Hemato-Oncology Unit, Heim Pal Children's Hospital, Budapest, Hungary., Kállay K; Division of Pediatric Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary., Kriván G; Division of Pediatric Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary., Barna G; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Bedics G; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Haltrich I; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Ottóffy G; Department of Pediatrics, University of Pécs Clinical Centre, Pécs, Hungary., Csernus K; Department of Pediatrics, University of Pécs Clinical Centre, Pécs, Hungary., Vojcek Á; Department of Pediatrics, University of Pécs Clinical Centre, Pécs, Hungary., Tiszlavicz LG; Department of Pediatrics and Pediatric Health Care Center, University of Szeged, Szeged, Hungary., Gábor KM; Department of Pediatrics and Pediatric Health Care Center, University of Szeged, Szeged, Hungary., Kelemen Á; Hemato-Oncology and Stem Cell Transplantation Unit, Velkey László Child's Health Center, Borsod-Abaúj-Zemplén County Central Hospital and University Teaching Hospital, Miskolc, Hungary., Hauser P; Hemato-Oncology and Stem Cell Transplantation Unit, Velkey László Child's Health Center, Borsod-Abaúj-Zemplén County Central Hospital and University Teaching Hospital, Miskolc, Hungary., Gaál Z; Department of Pediatric Hematology and Oncology, Institute of Pediatrics, University of Debrecen, Debrecen, Hungary., Szegedi I; Department of Pediatric Hematology and Oncology, Institute of Pediatrics, University of Debrecen, Debrecen, Hungary., Ujfalusi A; Department of Laboratory Medicine, University of Debrecen, Debrecen, Hungary., Kajtár B; Department of Pathology, University of Pécs Clinical Centre, Pécs, Hungary., Kiss C; Hemato-Oncology and Stem Cell Transplantation Unit, Velkey László Child's Health Center, Borsod-Abaúj-Zemplén County Central Hospital and University Teaching Hospital, Miskolc, Hungary., Matolcsy A; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary; Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Tímár B; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Kovács G; Department of Pediatrics, Semmelweis University, Budapest, Hungary., Alpár D; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Bödör C; HCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. Electronic address: bodor.csaba1@semmelweis.hu.
Jazyk:	angličtina
Zdroj:	The Journal of molecular diagnostics : JMD [J Mol Diagn] 2023 Aug; Vol. 25 (8), pp. 555-568. Date of Electronic Publication: 2023 Apr 22.
DOI:	10.1016/j.jmoldx.2023.04.004
Abstrakt:	Pediatric acute myeloid leukemia (AML) represents a major cause of childhood leukemic mortality, with only a limited number of studies investigating the molecular landscape of the disease. Here, we present an integrative analysis of cytogenetic and molecular profiles of 75 patients with pediatric AML from a multicentric, real-world patient cohort treated according to AML Berlin-Frankfurt-Münster protocols. Targeted next-generation sequencing of 54 genes revealed 17 genes that were recurrently mutated in >5% of patients. Considerable differences were observed in the mutational profiles compared with previous studies, as BCORL1, CUX1, KDM6A, PHF6, and STAG2 mutations were detected at a higher frequency than previously reported, whereas KIT, NRAS, and KRAS were less frequently mutated. Our study identified novel recurrent mutations at diagnosis in the BCORL1 gene in 9% of the patients. Tumor suppressor gene (PHF6, TP53, and WT1) mutations were found to be associated with induction failure and shorter event-free survival, suggesting important roles of these alterations in resistance to therapy and disease progression. Comparison of the mutational landscape at diagnosis and relapse revealed an enrichment of mutations in tumor suppressor genes (16.2% versus 44.4%) and transcription factors (35.1% versus 55.6%) at relapse. Our findings shed further light on the heterogeneity of pediatric AML and identify previously unappreciated alterations that may lead to improved molecular characterization and risk stratification of pediatric AML. (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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