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

Autores: Medina, A.; Jimenez, C.; Sarasquete, M. E. (Autor de correspondencia); Gonzalez, M.; Chillon, M. C.; Balanzategui, A. ; Prieto-Conde, I.; Garcia-Alvarez, M.; Puig, N. ; Gonzalez-Calle, V. ; Alcoceba, M.; Cuenca, I.; Barrio, S.; Escalante, F. ; Gutierrez, N. C.; Gironella, M.; Hernandez, M. T.; Sureda, A.; Oriol, A. ; Blade, J.; Lahuerta, J. J.; San Miguel Izquierdo, Jesús; Mateos, M. V.; Martinez-Lopez, J. ; Calasanz Abinzano, María José; Garcia-Sanz, R.
Título de la revista: BLOOD CANCER JOURNAL
ISSN: 2044-5385
Volumen: 10
Número: 2
Páginas: 14
Fecha de publicación: 2020
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.