A comprehensive analysis of common cytogenetic abnormalities in multiple myeloma: from basic research to clinical...

The significant heterogeneity of multiple myeloma (MM) profoundly impacts patient prognosis, with cytogenetic abnormalities serving as a core driver. Based on the International Myeloma Working Group and 2024 International Myeloma Society consensus, this study enrolled 52 newly diagnosed MM patients. Six cytogenetic abnormalities-RB1 deletion, D13S319 deletion, immunoglobulin heavy chain (IGH) translocation, 1q21 gain/amplification, P53 deletion, and 1p32 deletion-were detected using fluorescence in situ hybridisation. Integrating clinical data and immunohistochemical analysis, we investigated the clinical associations and prognostic significance of these abnormalities. Results demonstrated that the positive detection rate of cytogenetic abnormalities ranged from 11.5% to 46.2% and was significantly associated with advanced tumour stage [International Staging System, revised International Staging System (R-ISS), and R2-ISS]. Patients with cytogenetic abnormalities frequently exhibited adverse haematological parameters, including low haemoglobin and elevated β2-microglobulin and were associated with aggressive tumour biological behaviours such as enhanced anti-apoptotic capacity, high proliferation index, and increased microvessel density. Survival analysis confirmed that all abnormalities except IGH translocation significantly shortened both overall survival (OS) and progression-free survival (PFS), with P53 deletion identified as an independent risk factor for OS. Among patients receiving bortezomib, lenalidomide, and dexamethasone (VRd) induction therapy, those with cytogenetic abnormalities showed significantly lower deep response rates (complete response + very good partial response). According to the latest 'multiple-hit' definition, patients classified as 'triple hit' had significantly shorter OS and reduced response rates compared to those receiving VRd therapy. Furthermore, RB1 deletion or D13S319 deletion combined with other high-risk indicators further shortened PFS. These findings indicate that integrating expanded cytogenetic markers optimises MM risk stratification and provides a basis for individualised treatment strategies.