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Title: | Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients |
Author: | Medina, Alejandro Jiménez, Cristina Sarasquete, M. Eugenia González, Marcos Chillón, M. Carmen Balanzategui, Ana Prieto Conde, Isabel García Álvarez, María Puig, Noemí González Calle, Verónica Alcoceba, Miguel Cuenca, Isabel Barrio, Santiago Escalante, Fernando Gutiérrez, Norma C. Gironella, Mercedes Hernández, Miguel T. Sureda, Anna Oriol, Albert Bladé, J. (Joan) Lahuerta, Juan José San Miguel, Jesús F. Mateos, María Victoria Martínez López, Joaquín Calasanz, María José García Sanz, Ramón |
Keywords: | Mieloma múltiple Cèl·lules B Multiple myeloma B cells |
Issue Date: | 6-Feb-2020 |
Publisher: | Springer Nature |
Abstract: | Multiple 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41408-020-0283-8 |
It is part of: | Blood Cancer Journal, 2020, vol. 10, num. 14 |
URI: | http://hdl.handle.net/2445/173319 |
Related resource: | https://doi.org/10.1038/s41408-020-0283-8 |
ISSN: | 2044-5385 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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