E-Book

E-Book 3rd Congress

  • Molecular Progression and Multiple-Target Biomarkers in Multiple Myeloma: A Brief Review
  • Amin Hasanpour,1 Tahereh Kalantari,2,*
    1. Division of hematology and blood banking, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
    2. 1. Division of hematology and blood banking, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran 2. Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical


  • Introduction: Multiple myeloma (MM) is a cancer affecting plasma cells with different variations. It starts with monoclonal gammopathy of uncertain significance (MGUS), a pre-malignant stage that often goes unnoticed. MGUS progresses to MM at a rate of 1% per year. Asymptomatic or smoldering myeloma (SMM) is a condition where the level of plasma cells is above 10% or the monoclonal protein level is above 30 g/l. Standard-risk SMM patients have a 10% risk of progression to active myeloma for the first five years. The International Myeloma Working Group (IMWG) updated the definition of MM with three new criteria in addition to hypercalcemia, renal impairment, anemia, bone disease (CRAB criteria) for therapy initiation, including plasma cell infiltration >60%, serum free light chain level/ratio >100mg/l, and the presence of focal lesions on advanced imaging. The treatment of multiple myeloma typically includes the use of chemotherapeutic medications, although relapse is common in the majority of cases. Research has led to newer markers for diagnosis, prognosis, and therapeutics. This review discusses molecular progression from MGUS to MM and summarizes conventional and new approaches for better management, considering patient convenience.
  • Methods: In this review, we demonstrated searches with PubMed, Google Scholar, and medical journals identifying articles relevant to our topic.
  • Results: 1. Molecular progression MM is caused by molecular events like chromosomal translocations and hyperdiploidy. About 55% of MM patients show recurrent chromosomal translocations at the immunoglobin heavy chain (IgH) locus at 14q32. The most common translocations are t(11;14) and t(4;14). In multiple myeloma (MM), chromosomal hyperdiploidy is seen in up to 50% of patients, leading to abnormal gene expression of the cyclin D family and cell growth. In MGUS, genetic abnormalities increase malignant plasma cells to >10% of bone marrow mononuclear cells. MM cells acquire Ras family oncogene mutations involving APOBEC3B, and c-Myc overexpression occurs in MGUS to MM progression. DNA hypomethylation may accelerate disease progression. In the terminal stage of myeloma, MM cells exhibit stroma-independent growth, sustained by the activation of NF-kB. In terminal-stage myeloma, genes encoding NF-kB pathway inhibitors are lost, and there are extensive structural abnormalities of chromosomes, such as complex translocations involving the c-Myc gene, duplication of chromosome 1q, and deletions of 1p32 or 17p13. TP53 mutations usually occur with 17p deletion, especially in refractory cases, and they have oncogenic functions, including up-regulation of c-Myc and genes encoding proteasome subunits, which induce anti-cancer drug resistance. 2. Biomarkers MM is diagnosed using nongenomic and genomic biomarkers. Nongenomic biomarkers include staging systems such as DSS, ISS, and IRSS, plasma cell percentage, chromosomal abnormalities, serum protein electrophoresis, urinary Bence-Jones protein, FLC, and imaging techniques. Genomic biomarkers include IFISH and GEP. Commonly used markers for diagnosing and staging MM include plasma cell percentage, β2 microglobulin, albumin, and Bence Jones proteins. Newer markers like ECM proteins, circulatory tumor cells (CT cells), micro RNAs, and cell-free (cf) DNA offer a non-invasive approach to detecting MM and can improve prognostic accuracy. Immunotherapy using immune-modulating drugs like lenalidomide is followed by monoclonal antibodies such as daratumumab for treating relapsed cases of MM. Certain proteins like amyloid A protein, vitamin D-binding protein isoform-1, and HSP 90 are dysregulated in MM patients and could serve as markers for diagnosis or prognosis prediction. Liquid biopsy is a non-invasive method to evaluate plasma cells and nucleic acids for efficiently detecting MM. This technique offers a comprehensive understanding of the disease's molecular profile in the peripheral circulation, making it a promising tool for diagnosis and treatment response assessments.
  • Conclusion: It's important to have a good understanding of the molecular mechanisms of MM in order to fully comprehend its progression. It also suggests that both nongenomic and genomic biomarkers should be used to diagnose MM, and newer markers like CT cells and cfDNA could be used to detect MM non-invasively with improved prognostic accuracy. The article also discusses the use of immunotherapy and monoclonal antibodies in treating relapsed MM cases. However, there is still a lack of validated biomarkers that can predict the risk of progression to symptomatic disease for both MGUS and SMM, indicating the need for more research in this field. Overall, this review provides valuable insights into the diagnosis, management, and treatment of MM, emphasizing the necessity for continued research to improve patient outcomes.
  • Keywords: MM, MGUS, SMM, molecular progression, Biomarkers