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- Title
Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients.
- Authors
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, Joan
- 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.
- Subjects
MULTIPLE myeloma treatment; IMMUNOGLOBULINS; B cells; PROGRESSION-free survival; UNIVARIATE analysis
- Publication
Blood Cancer Journal, 2020, Vol 10, Issue 2, p1
- ISSN
2044-5385
- Publication type
Article
- DOI
10.1038/s41408-020-0283-8