4 research outputs found
Molecular profiling of immunoglobulin heavychain 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 characterization of complete heavychain 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 (â„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: 0.361â0.845, p = 0.006), as well as prolonged overall
survival rates for patients with hypermutation â„7% (HR: 0.291, 95% CI: 0.137â0.618, 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
Molecular profiling of immunoglobulin heavychain 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 characterization of complete heavychain 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 (â„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: 0.361â0.845, p = 0.006), as well as prolonged overall
survival rates for patients with hypermutation â„7% (HR: 0.291, 95% CI: 0.137â0.618, 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