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Article

Capture-Based Next-Generation Sequencing Improves the Identification of Immunoglobulin/T-Cell Receptor Clonal Markers and Gene Mutations in Adult Acute Lymphoblastic Leukemia Patients Lacking Molecular Probes

1
Hematology and Bone Marrow Transplant Unit, Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, 24127 Bergamo, Italy
2
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milano, Italy
3
Hematology Unit, dell’Angelo Hospital and SS. Giovanni and Paolo Hospital, 30174 Venezia Mestre, Italy
4
Department of Oncology and Hematology, Università degli Studi di Milano, 20122 Milano, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(6), 1505; https://doi.org/10.3390/cancers12061505
Received: 28 April 2020 / Revised: 23 May 2020 / Accepted: 5 June 2020 / Published: 9 June 2020
(This article belongs to the Special Issue Hematologic Malignancy)
The monitoring of minimal residual disease (MRD) in Philadelphia-negative acute lymphoblastic leukemia (ALL) requires the identification at diagnosis of immunoglobulin/T-cell receptor (Ig/TCR) rearrangements as clonality markers. Aiming to simplify and possibly improve the patients’ initial screening, we designed a capture-based next-generation sequencing (NGS) panel combining the Ig/TCR rearrangement detection with the profiling of relevant leukemia-related genes. The validation of the assay on well-characterized samples allowed us to identify all the known Ig/TCR rearrangements as well as additional clonalities, including rare rearrangements characterized by uncommon combinations of variable, diversity, and joining (V-D-J) gene segments, oligoclonal rearrangements, and low represented clones. Upon validation, the capture NGS approach allowed us to identify Ig/TCR clonal markers in 87% of a retrospective cohort (MRD-unknown within the Northern Italy Leukemia Group (NILG)-ALL 09/00 clinical trial) and in 83% of newly-diagnosed ALL cases in which conventional method failed, thus proving its prospective applicability. Finally, we identified gene variants in 94.7% of patients analyzed for mutational status with the same implemented capture assay. The prospective application of this technology could simplify clonality assessment and improve standard assay development for leukemia monitoring, as well as provide information about the mutational status of selected leukemia-related genes, potentially representing new prognostic elements, MRD markers, and targets for specific therapies. View Full-Text
Keywords: acute lymphoblastic leukemia; next-generation sequencing; minimal residual disease acute lymphoblastic leukemia; next-generation sequencing; minimal residual disease
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MDPI and ACS Style

Cavagna, R.; Guinea Montalvo, M.L.; Tosi, M.; Paris, M.; Pavoni, C.; Intermesoli, T.; Bassan, R.; Mosca, A.; Rambaldi, A.; Spinelli, O. Capture-Based Next-Generation Sequencing Improves the Identification of Immunoglobulin/T-Cell Receptor Clonal Markers and Gene Mutations in Adult Acute Lymphoblastic Leukemia Patients Lacking Molecular Probes. Cancers 2020, 12, 1505. https://doi.org/10.3390/cancers12061505

AMA Style

Cavagna R, Guinea Montalvo ML, Tosi M, Paris M, Pavoni C, Intermesoli T, Bassan R, Mosca A, Rambaldi A, Spinelli O. Capture-Based Next-Generation Sequencing Improves the Identification of Immunoglobulin/T-Cell Receptor Clonal Markers and Gene Mutations in Adult Acute Lymphoblastic Leukemia Patients Lacking Molecular Probes. Cancers. 2020; 12(6):1505. https://doi.org/10.3390/cancers12061505

Chicago/Turabian Style

Cavagna, Roberta, Marie L. Guinea Montalvo, Manuela Tosi, Michela Paris, Chiara Pavoni, Tamara Intermesoli, Renato Bassan, Andrea Mosca, Alessandro Rambaldi, and Orietta Spinelli. 2020. "Capture-Based Next-Generation Sequencing Improves the Identification of Immunoglobulin/T-Cell Receptor Clonal Markers and Gene Mutations in Adult Acute Lymphoblastic Leukemia Patients Lacking Molecular Probes" Cancers 12, no. 6: 1505. https://doi.org/10.3390/cancers12061505

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