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

Adult Aged Aged, 80 and over Biomarkers, Tumor / genetics Female Follow-Up Studies Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Rearrangement Humans Immunoglobulin Heavy Chains / genetics Immunoglobulin Variable Region / genetics Male Middle Aged Multigene Family Multiple Myeloma / genetics Prognosis

Journal

Blood cancer journal

ISSN: 2044-5385

Titre abrégé: Blood Cancer J

Pays: United States

ID NLM: 101568469

Informations de publication

Date de publication:
06 02 2020

Historique:

received: 04 09 2019

accepted: 21 01 2020

revised: 16 01 2020

entrez: 8 2 2020

pubmed: 8 2 2020

medline: 31 10 2020

Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41408-020-0283-8 PMID: 32029700 PMC: PMC7004993

pubmed: 32029700

doi: 10.1038/s41408-020-0283-8

pii: 10.1038/s41408-020-0283-8

pmc: PMC7004993

doi:

Substances chimiques

Biomarkers, Tumor 0

Immunoglobulin Heavy Chains 0

Immunoglobulin Variable Region 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

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