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E-Book 3rd Congress

  • Non-Invasive Monitoring of Multiple Myeloma Using Plasma Cell-Free DNA
  • Mohadeseh Ramezani,1 Sina Eshaghi,2 Mohammad Hossein Ahmadi,3,*
    1. Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Science, Mashhad, Iran.
    2. Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Science, Mashhad, Iran.
    3. Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Science, Mashhad, Iran.


  • Introduction: Multiple myeloma (MM) is a malignant clonal plasma cell tumor with a median survival of 5 years, characterized by malignant proliferation of clonal plasma cells in the bone marrow and secretion of monoclonal immunoglobulin (M protein). Multiple myeloma is the second most common malignant hematologic tumor after lymphoma. The term “Cell-free DNA (cfDNA)” refers to fragmented DNA found in the non-cellular component of the blood. In healthy people, small amounts of cfDNA from normal cells are present in plasma. The aim of this study was to evaluate the potential of cell-free DNA released from cancer cells into patient biofluids, as an accurate biomarker for the diagnosis, prognostic assessment and monitoring of multiple myeloma disease.
  • Methods: The search was conducted in PubMed and Google Scholar databases using keywords such as multiple myeloma and cell free DNA, and articles published between 2020 and 2023 were evaluated.
  • Results: Studies have shown that there is an increase in cfDNA in the body fluids of people with multiple myeloma, and by examining the mutations that have occurred in the genome sequence, the presence of this disease, prognosis and minimal residual disease (MRD) can be assessed. Next-generation sequencing (NGS) using cfDNA has been proposed to investigate the profile of the GEP70 gene (70 gene expression profile, as a tool to predict disease recurrence and survival outcome) as well as ALU115 and ALU247 gene fragments. ALU tandem repeats, the most common sequence in the human genome, make up 10% of the human genome and are typically 300 nucleotides long. Because their methylation level is lower than that of coding genes, they are not easily affected by other factors, making them easier to identify. The concentration of ALU247 (long fragments) and ALU115 (short fragments) in the MM patients is significantly higher than that of healthy individuals, which is due to the large amount of cell death and the inability of the liver to destroy these DNA fragments. Also, the ratio of the number of ALU115 genome (representing total cfDNA) to ALU247 genome (representing free DNA release from non-apoptotic cells) in the cfDNA integrity assay, representing the number bone marrow plasma cells, is increased in MM. It was also found that the levels of ALU247, ALU115, and cfDNA integrity after chemotherapy were lower than before chemotherapy. In addition, recent studies show that minimal residual disease (MRD) Monitoring by next-generation sequencing (NGS) of cfDNA has achieved sensitivity levels of 10^-6 and can be applied to the vast majority of MM patients.
  • Conclusion: According to the impossibility of repeating bone marrow sampling as an invasive method and the patchy distribution of cells in the bone marrow, at the same time due to acceptable sensitivity, the possibility of transfer at room temperature, the ease of examination of cfDNA that is present even in peripheral blood and also, due to significant progress in the diagnostic ways of mutations in the genome sequence, screening of cfDNA samples as a non-invasive method for disease diagnosis, prognostic assessment and monitoring of MRD is recommended.
  • Keywords: Cell-free DNA; multiple myeloma; minimal residual disease (MRD)