Abstract
Multiple myeloma (MM) is a heterogeneous disease, the full understanding of whose pathogenesis remains elusive. While B-cell receptors are known to play a pivotal role in myeloma pathogenesis, the characterization of immunoglobulin heavy-chain (IGH) gene repertoire and their clinical significance in Chinese patients has not been fully explored. In this study, we analyzed the profiling of clonal IGH gene rearrangements via NGS assay, and its cytogenetic abnormalities by FISH in a cohort of 301 Chinese patients with newly diagnosed MM. We identified a particular subgroup, which was characterized by a marked overrepresentation of IGHV4-39. Additionally, IGHV4-39 was correlated with a higher somatic hypermutation rate and shorter HCDR3 length. Notably, IGHV4-39 was significantly more prevalent in patients with high-risk cytogenetic abnormalities, particularly the recurrent IGH translocations involving t(4;14). Our findings, represented the largest IGH data in MM series from Asia, and investigated the association between specific IGHV and cytogenetic alterations in Chinese MM patients for the first time.