Abstract
This review aims to provide a comprehensive overview of recent advances in the genomics of multiple myeloma and their clinical implications. Multiple myeloma is a hematologic malignancy originating from bone marrow plasma cells, characterized by the infiltration of pathological plasma cells, osteolytic bone lesions, and the presence of monoclonal immunoglobulins in serum and/or urine. Multiple myeloma exhibits significant genetic heterogeneity, which is the core reason for the considerable variability in patient prognosis, differential treatment responses, and the eventual development of drug resistance. In recent years, with the rapid development of high-throughput sequencing technologies (such as next-generation sequencing, single-cell sequencing) and bioinformatics, our understanding of genomic abnormalities in multiple myeloma has reached an unprecedented depth. Importantly, these genomic abnormalities have begun to directly inform clinical practice, holding significant promise particularly in risk stratification, treatment selection, minimal residual disease monitoring, and early warning of relapse. This review systematically outlines the latest research progress in the field of multiple myeloma genomics. It focuses on elucidating the function and clinical significance of key driver gene mutations (eg, NRAS/KRAS, TP53, MYC), delves into the roles of copy number variations (particularly 1q21 amplification), epigenetic dysregulation (including DNA methylation, histone modifications), and non-coding RNAs in multiple myeloma pathogenesis. Furthermore, this review looks forward to future developments, including targeted and immunotherapeutic strategies guided by genomics, as well as the use of liquid biopsy for minimal residual disease monitoring, offering new insights into the precision diagnosis and treatment of multiple myeloma.