Multiple myeloma is the second most common hematological malignancy characterized by focal lesions of malignant plasma cells in the bone marrow. These lesions contain subclones that directly influence survival of patients. Bone marrow biopsies are single-site biopsies and thus cannot contain all information about the tumor. In contrast, liquid biopsies analyze circulating cells and molecules that are secreted from all sites of the tumor. Long noncoding RNA molecules are one class of these molecules. We performed a two-phase biomarker study investigating lncRNA expression profiles in exosomes of peripheral blood serum of newly diagnosed multiple myeloma (MM) patients, monoclonal gammopathy of undetermined significance (MGUS) patients in comparison with healthy donors (HD). Surprisingly, this analysis revealed dysregulation of only one exosomal lncRNA PRINS in MM vs HD. Overall, MM and MGUS patients were distinguished from HD with sensitivity of 84.9% and specificity of 83.3%. Our study suggests a possible diagnostic role for exosomal lncRNA PRINS in monoclonal gammopathies patients.

Unlike bone marrow biopsies, liquid biopsies represent a gentler, more accessible, less painful, repeatable and more comprehensive approach to get biologically relevant information about the entire tumor but also about treatment response and level of minimal residual disease. This is all possible since peripheral blood contains not only circulating tumor cells but also many circulating molecules of nucleic acids (microRNA, cell-free DNA, long non-coding RNA etc.). Multiple myeloma is a genetically heterogeneous disease characterized by multifocal tumor deposits in the bone marrow but also focal lesions elsewhere. Single-site biopsy of the bone marrow creates a sampling bias that provides a limited molecular profile as the biopsy cannot capture all subclones. Moreover, during disease progression and treatment, molecular profile is changed and subclones of multiple myeloma cells resistant to treatment are formed. Likewise, various clones found in extramedullary sites that are not present in the bone marrow respond differently to treatment directly influencing survival of patients. Thus, liquid biopsies seem to be a relevant and necessary next step for diseases such as multiple myeloma.Key words: multiple myeloma - minimal residual disease - prognosis - liquid biopsies - cell-free DNA - non-coding RNA.

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