Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients
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Published:2020-02
Issue:2
Volume:10
Page:
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ISSN:2044-5385
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Container-title:Blood Cancer Journal
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language:en
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Short-container-title:Blood Cancer J.
Author:
Medina AlejandroORCID, Jiménez Cristina, Sarasquete M. Eugenia, González Marcos, Chillón M. Carmen, Balanzategui Ana, Prieto-Conde IsabelORCID, García-Álvarez María, Puig Noemí, González-Calle Verónica, Alcoceba MiguelORCID, Cuenca Isabel, Barrio Santiago, Escalante Fernando, Gutiérrez Norma C., Gironella Mercedes, Hernández Miguel T., Sureda Anna, Oriol Albert, Bladé Joan, Lahuerta Juan-José, San Miguel Jesús F., Mateos María-VictoriaORCID, Martínez-López Joaquín, Calasanz María-JoséORCID, García-Sanz RamónORCID
Abstract
AbstractMultiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of IGHV3, IGHD2 and IGHD3, as well as IGHJ4 gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of IGHD2 and IGHD3 groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using IGHD2/IGHD3 groups (HR: 0.552, 95% CI: 0.361−0.845, p = 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618, p = 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers.
Funder
EC | Directorate-General for Employment, Social Affairs and Inclusion | European Social Fund Fundación Española de Hematología y Hemoterapia Ministry of Economy and Competitiveness | Instituto de Salud Carlos III
Publisher
Springer Science and Business Media LLC
Subject
Oncology,Hematology
Reference54 articles.
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