Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients

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 cha...

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Detalles Bibliográficos
Autores: Medina, Alejandro, Jiménez, Cristina, Sarasquete, Maria 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/173319
Acceso en línea:https://hdl.handle.net/2445/173319
Access Level:acceso abierto
Palabra clave:Mieloma múltiple
Cèl·lules B
Multiple myeloma
B cells
Descripción
Sumario: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.

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