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.
Highlights
Myeloid neoplasms (MN) constitute a group of hematological diseases that include acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) [1]
We evaluated the use of two enrichment-capture gene panels for the detection of gene variants, copy number variants (CNV) and translocations that are frequently present in myeloid neoplasms (MN)
Patients with MDS, polycythemia vera (PV), essential thrombocythemia (ET), and MDS/MPN were only included if they were considered suitable for therapy or included in a clinical trial; patients were not consecutive
Summary
Myeloid neoplasms (MN) constitute a group of hematological diseases that include acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) [1]. Myeloid NGS panels can be applied to perform a complete analysis of genetic alterations in a single approach. These alterations are mainly single-nucleotide variants and small insertions and deletions, some myeloid gene panels cover copy number variants (CNV) and translocations. NGS myeloid panels are being implemented in routine diagnosis, there is no standard approach; features such as gene selection, sequencing platform, read depth and variant analysis can differ between laboratories. Myeloid panels are not usually designed to detect large alterations, mainly reported in whole genome NGS studies, which main limitation are their low depth and the difficulty to include them in daily clinical routine [12,13,14,15,16]
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