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

Krizsán, Szilvia and Péterffy, Borbála and Egyed, Bálint and Nagy, Tibor and Sebestyén, Endre and Hegyi, Lajos and Jakab, Zsuzsanna and Erdélyi, Dániel and Müller, Judit and Péter, György and Csanádi, Krisztina and Kállay, Krisztián and Kriván, Gergely and Barna, Gábor and Bedics, Gábor and Haltrich, Irén and Ottóffy, Gábor and Csernus, Katalin and Vojcek, Ágnes and Tiszlavicz, Lilla and Gábor, Krisztina and Kelemen, Ágnes and Hauser, Péter and Gaál, Zsuzsanna and Szegedi, István and Ujfalusi, Anikó and Kajtár, Béla and Kiss, Csongor and Matolcsy, András and Timár, Botond and Kovács, Gábor and Alpár, Donát and Bödör, Csaba (2023) Next-Generation Sequencing–Based Genomic Profiling of Children with Acute Myeloid Leukemia. JOURNAL OF MOLECULAR DIAGNOSTICS, 25 (8). pp. 555-568. ISSN 1525-1578 (print); 1943-7811 (online)

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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.

Item Type: Article
Subjects: R Medicine / orvostudomány > RB Pathology / patológia, kórtan
R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkológia
R Medicine / orvostudomány > RJ Pediatrics / gyermekgyógyászat
Depositing User: Dr Donat Alpar
Date Deposited: 12 Sep 2023 08:30
Last Modified: 13 Sep 2023 10:53

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