BACKGROUND: Multiple myeloma (MM) represents the second most common hematological malignancy characterized by the infiltration of the bone marrow by plasma cells that produce monoclonal immunoglobulin. While the quality and length of life of MM patients have significantly increased, MM remains a hard-to-treat disease; almost all patients relapse. As MM is highly heterogenous, patients relapse at different times. It is currently not possible to predict when relapse will occur; numerous studies investigating the dysregulation of non-coding RNA molecules in cancer suggest that microRNAs could be good markers of relapse. RESULTS: Using small RNA sequencing, we profiled microRNA expression in peripheral blood in three groups of MM patients who relapsed at different intervals. In total, 24 microRNAs were significantly dysregulated among analyzed subgroups. Independent validation by RT-qPCR confirmed changed levels of miR-598-3p in MM patients with different times to relapse. At the same time, differences in the mass spectra between groups were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry. All results were analyzed by machine learning. CONCLUSION: Mass spectrometry coupled with machine learning shows potential as a reliable, rapid, and cost-effective preliminary screening technique to supplement current diagnostics.

• Klíčová slova
• Liquid biopsy, MALDI-TOF MS, Machine learning, Multiple myeloma, Relapse, Small RNA seq, microRNA,
• Publikační typ
• časopisecké články MeSH

Multiple myeloma is a plasma cell malignancy characterized by an abnormal increase in monoclonal immunoglobulins. Despite significant advances in treatment, some patients progress to more aggressive forms of multiple myeloma, including extramedullary disease or plasma cell leukemia. Although the exact molecular mechanisms are not known, several studies have confirmed the involvement of small extracellular vesicle-enriched microRNAs in multiple myeloma progression. Therefore, we performed expression profiling of these molecules in bone marrow plasma of multiple myeloma, extramedullary disease, and plasma cell leukemia patients using small RNA sequencing to identify novel molecules involved in disease pathogenesis. In total, 42 microRNAs were significantly dysregulated among analyzed subgroups. Independent validation by RT-qPCR confirmed elevated levels of miR-140-3p, miR-584-5p, miR-191-5p, and miR-143-3p in multiple myeloma patients compared to extramedullary disease and plasma cell leukemia patients. Subsequent statistical analysis revealed significant correlations between patient clinical characteristics or flow cytometry parameters and microRNA expression. These results indicate that dysregulation of microRNAs could contribute to multiple myeloma progression.

• Klíčová slova
• extramedullary disease, microRNAs, multiple myeloma, plasma cell leukemia, small RNA sequencing, small extracellular vesicles,
• MeSH
• dospělí MeSH
• extracelulární vezikuly * metabolismus   genetika   patologie   MeSH
• kostní dřeň * patologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• mnohočetný myelom * genetika   patologie   metabolismus   MeSH
• nádorové biomarkery genetika   MeSH
• plazmatické buňky metabolismus   MeSH
• plazmocelulární leukemie * genetika   patologie   metabolismus   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA * MeSH
• nádorové biomarkery MeSH