Advancements in Molecular Diagnostics of Multiple Myeloma: Fundamental Insight to a Path for Better Treatment

Multiple Myeloma (MM) is a malignancy of antibody-secreting, terminally differentiated B cells that home to and expand in the bone marrow, with symptoms related to anemia, immunosuppression, bone destruction, and renal failure. Molecular diagnosis plays a crucial role in the identification and characterization of the disease, guiding treatment decisions and prognostic assessments in order to examine MM from a molecular basis in genetic form and the pathways of the malignant event process, so as to reach a suitable summary of the events at the molecular level. Methods: The basis of collecting information in fallowing study on the molecular basis of MM, methods including Next-Generation Sequencing (NGS) and cytogenetic Analysis such as Fluorescence In Situ Hybridization (FISH) have been widely used. NGS was specifically used to illustrate KRAS, NRAS, BRAF and TP۵۳ expression profiles. Along with investigations on a smaller scale using more well-known methods, Plasma Cell- Free DNA (cfDNA) Analysis has also been used to investigate gene mutations in blood samples. Monoclonal Protein Detection methods including Serum Protein Electrophoresis (SPEP) to detect M-proteins produced by malignant plasma cells and Immunofixation Electrophoresis (IFE) was also applied to determine the level of protein secretion. Recent studies on different approaches show that Digital Droplet PCR (ddPCR) is also performed for quantifying specific DNA sequence which is useful for detecting minimal Residual Disease (MDR), gene expression analysis, variant detection and treatment monitoring. The final assessments can be conducted by Artificial Intelligence (AI) and machine learning protocols. Results: The universal activation of ۱ of the ۳ cyclin D genes is consistent with this being an initiating event in MM. Nonhyperdiploid MM, is characterized by transcriptional activation of CCND۱, CCND۳, MAF, MAFB, or FGFR۳/MMSET genes (resulting from translocations involving the immunoglobulin heavy chain locus). While hyperdiploidy and CCND۱ activation confer a favorable prognosis, MAF, MAFB, or FGFR۳/MMSET activation and deletion of chromosomes ۱۳ and ۱۷ are associated with poor prognosis. Mutation of TP۵۳, NRAS and KRAS can contribute to disease progression and resistance to various therapies. Although high-dose therapy has markedly improved MM prognosis, individual patient's survival remains variable and cannot be accurately predicted. In MM, microarray profiling approach also has identified genes involved in pathogenesis pathways. Conclusion: The molecular diagnosis of Multiple Myeloma is a multifaceted approach that combines various techniques to provide a comprehensive understanding of the disease's genetic and molecular characteristics. This information is critical for personalized treatment strategies and improving patient outcomes. Regular updates in guidelines and research continue to refine these diagnostic methods. Recent studies on the molecular and cellular processes of MM show that genetic disorders, including translocation and deletion, have a vital effect on the process of disease by inhibiting some cellular pathways. By controlling specific genes and its mutations such as KRAS and TP۵۳, it can be prevented, despite the fact that this disease has become widespread in the world today.

کلیدواژه ها:

Multiple Myeloma ، Molecular Diagnosis ، KRAS ، Minimal Residual Disease