Next-Generation Sequencing Improves Diagnosis, Prognosis and Clinical Management of Myeloid Neoplasms.

Carbonell D1,2, Suárez-González J3,4, Chicano M5,6, Andrés-Zayas C7,8, Triviño JC9, Rodríguez-Macías G10, Bastos-Oreiro M11,12, Font P13,14, Ballesteros M15, Muñiz P16,17, Balsalobre P18,19, Kwon M20,21, Anguita J22,23, Díez-Martín JL24,25,26, Buño I27,28,29, Martínez-Laperche C30,31.

Author information

1: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. diego.carbonell@iisgm.com.
2: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. diego.carbonell@iisgm.com.
3: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. julia.suarez@iisgm.com.
4: Genomics Unit, Gregorio Marañón General University Hospital, IiSGM, 28007 Madrid, Spain. julia.suarez@iisgm.com.
5: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. maria.chicano@salud.madrid.org.
6: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. maria.chicano@salud.madrid.org.
7: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. cristina.andres@iisgm.com.
8: Genomics Unit, Gregorio Marañón General University Hospital, IiSGM, 28007 Madrid, Spain. cristina.andres@iisgm.com.
9: Sistemas Genómicos, 46980 Valencia, Spain. jc.trivino@sistemasgenomicos.com.
10: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. gabriela.rodriguez@salud.madrid.org.
11: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. marianabeatriz.bastos@salud.madrid.org.
12: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. marianabeatriz.bastos@salud.madrid.org.
13: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. patricia.font@salud.madrid.org.
14: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. patricia.font@salud.madrid.org.
15: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. monica.ballesteros@salud.madrid.org.
16: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. paula.muniz@iisgm.com.
17: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. paula.muniz@iisgm.com.
18: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. pascual.balsalobre@salud.madrid.org.
19: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. pascual.balsalobre@salud.madrid.org.
20: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. mi.kwon@salud.madrid.org.
21: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. mi.kwon@salud.madrid.org.
22: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. javier.anguita@salud.madrid.org.
23: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. javier.anguita@salud.madrid.org.
24: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. jdiezm@salud.madrid.org.
25: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. jdiezm@salud.madrid.org.
26: Department of Medicine, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain. jdiezm@salud.madrid.org.
27: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. ismaelbuno@iisgm.com.
28: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. ismaelbuno@iisgm.com.
29: Genomics Unit, Gregorio Marañón General University Hospital, IiSGM, 28007 Madrid, Spain. ismaelbuno@iisgm.com.
30: Department of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, Spain. cmartinezl@salud.madrid.org.
31: Gregorio Marañón Health Research Institute (IiSGM), 28007 Madrid, Spain. cmartinezl@salud.madrid.org.

Abstract

Molecular diagnosis of myeloid neoplasms (MN) is based on the detection of multiple genetic alterations using various techniques. Next-generation sequencing (NGS) has been proved as a useful method for analyzing many genes simultaneously. In this context, we analyzed diagnostic samples from 121 patients affected by MN and ten relapse samples from a subset of acute myeloid leukemia patients using two enrichment-capture NGS gene panels. Pathogenicity classification of variants was enhanced by the development and application of a custom onco-hematology score. A total of 278 pathogenic variants were detected in 84% of patients. For structural alterations, 82% of those identified by cytogenetics were detected by NGS, 25 of 31 copy number variants and three out of three translocations. The detection of variants using NGS changed the diagnosis of seven patients and the prognosis of 15 patients and enabled us to identify 44 suitable candidates for clinical trials. Regarding AML, six of the ten relapsed patients lost or gained variants, comparing with diagnostic samples. In conclusion, the use of NGS panels in MN improves genetic characterization of the disease compared with conventional methods, thus demonstrating its potential clinical utility in routine clinical testing. This approach leads to better-adjusted treatments for each patient.