Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: the PETHEMA NGS-AML project

• Published in: Haematologica (Roma) Vol. 106; no. 12; pp. 3079 - 3089
• Main Authors: Sargas, Claudia, Ayala, Rosa, Chillón, María Carmen, Larráyoz, María J., Carrillo-Cruz, Estrella, Bilbao, Cristina, Yébenes-Ramírez, Manuel, Llop, Marta, Rapado, Inmaculada, García-Sanz, Ramón, Vázquez, Iria, Soria, Elena, Florido-Ortega, Yanira, Janusz, Kamila, Botella, Carmen, Serrano, Josefina, Martínez-Cuadrón, David, Bergua, Juan, Amigo, Mari Luz, Martínez-Sánchez, Pilar, Tormo, Mar, Bernal, Teresa, Herrera-Puente, Pilar, García, Raimundo, Algarra, Lorenzo, Sayas, María J., Costilla-Barriga, Lisette, Pérez-Santolalla, Esther, Marchante, Inmaculada, Lavilla-Rubira, Esperanza, Noriega, Víctor, Alonso-Domínguez, Juan M., Sanz, Miguel Á., Sánchez-Garcia, Joaquín, Gómez-Casares, María T., Pérez-Simón, José A., Calasanz, María J., González-Díaz, Marcos, Martínez-López, Joaquín, Barragán, Eva, Montesinos, Pau
• Format: Journal Article
• Language: English
• Published: Italy Fondazione Ferrata Storti 01.12.2021; Ferrata Storti Foundation
• Subjects: High-Throughput Nucleotide Sequencing; Humans; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - genetics; Mutation; Recurrence
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2020.263806

Next-generation sequencing (NGS) has recently been introduced to efficiently and simultaneously detect genetic variations in acute myeloid leukemia (AML). However, its implementation in the clinical routine raises new challenges focused on the diversity of assays and variant reporting criteria. In order to overcome this challenge, the PETHEMA group established a nationwide network of reference laboratories aimed to deliver molecular results in the clinics. We report the technical cross-validation results for NGS panel genes during the standardization process and the clinical validation in 823 samples of 751 patients with newly diagnosed or refractory/relapse AML. Two cross-validation rounds were performed in seven nationwide reference laboratories in order to reach a consensus regarding quality metrics criteria and variant reporting. In the pre-standardization cross-validation round, an overall concordance of 60.98% was obtained with a great variability in selected genes and conditions across laboratories. After consensus of relevant genes and optimization of quality parameters the overall concordance rose to 85.57% in the second cross-validation round. We show that a diagnostic network with harmonized NGS analysis and reporting in seven experienced laboratories is feasible in the context of a scientific group. This cooperative nationwide strategy provides advanced molecular diagnostic for AML patients of the PETHEMA group (clinicaltrials gov. Identifier: NCT03311815).