Three-Dimensional Organization of Telomeres: An Emerging Prognostic Biomarker in Multiple Myeloma

A crucial role of genome instability and telomeric dysfunction was demonstrated in multiple cancers, including multiple myeloma (MM). MM accounts for approximately 10% of all hematologic malignancies and includes asymptomatic pre-malignant monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Due to the highly heterogeneous nature of the disease, there is an ongoing need for precise risk stratification and subsequent development of risk-adapted treatment strategies at every stage of disease and during disease progression. Telomere numbers, intensity, aggregates, and spatial arrangement within the nucleus were identified as prognostic biomarkers. Recent studies demonstrated that the three-dimensional (3D) analysis of key telomeric parameters is a reliable marker of the high risk of relapse in newly diagnosed MM (NDMM) patients and can predict the risk of progression of SMM patients. Telomeric parameters of malignant MM cells from the peripheral blood and bone marrow were similar, suggesting that 3D telomere profiling may assess MRD in liquid biopsies of MM patients. This review focuses on the prognostic value of 3D telomere profiling in MM. 3D spatial telomere analysis may potentially address a critical unmet clinical need in managing MM and, if incorporated into current guidelines, help to accurately predict disease status, progression risk, overall survival, and response to treatment.