IMPACT OF MULTIPLE MYELOMA: REVEALING CLINICAL AND GENETIC ASPECTS

Abstract

Introduction: Multiple myeloma (MM) is a neoplastic disease of plasma cells, the second most prevalent hematological cancer in Brazil, characterized by infiltration of the bone marrow by differentiated B lymphocytes (plasma cells) and progressive destruction of bone tissue. The pathology arises from an asymptomatic pre-malignant disorder and involves multifactorial components that result in MM. Objective: This study addresses the impact of multiple myeloma (MM), focusing on essential clinical and genetic aspects to understand its pathogenesis and impact on public health. Materials and methods: This study critically reviewed current guidelines on diagnosis, risk stratification, and treatment of multiple myeloma (MM). Using databases such as PubMed, Scopus, and Google Scholar, articles published from 2020 to 2022 were selected, including systematic reviews, meta-analyses, observational studies, and relevant clinical trials. The focus was on advances in molecular genetics. Results: Multiple myeloma (MM) begins from an asymptomatic precursor stage, relating complex genetic and microenvironmental changes that transform plasma cells into a malignant neoplasm. It was reported that its silencing suppressed cell proliferation and increased apoptosis by transcriptionally regulating the miRNA hsa-miR138-5p, targeting caspase-3, a potential target for the early diagnosis and treatment of MM. The KIAA1191 gene was associated with improved overall survival and progression-free survival. Furthermore, its high expression suppressed the proliferation and migration of MM cells and had a synergistic effect with bortezomib on the cells’ proliferation capacity. Initial therapies include VRd or Dara-VRd, followed by autologous stem cell transplantation (ASCT) in suitable candidates. Discussion: The clinical findings of this study showed that clinical history and investigation of the initial symptoms are needed. Multiple myeloma is more common in men above 65 years. The main symptoms are bone pain, anemia, leukocyte dysfunction and renal function alterations. To confirm the diagnosis, some additional tests are needed for therapeutic planning, including prothrombin time, activated partial thromboplastin time, fibrinogen, d-dimer, total bilirubin and fractions, alkaline phosphatase, transaminases and gamma-gt. Conclusion: This research underscores the complexity of multiple myeloma (MM) and the importance of early diagnosis and personalized treatment, beginning from an asymptomatic precursor stage with genetic and microenvironmental changes that transform plasma cells into malignant neoplasms. Initially, the progression from monoclonal gammopathy of undetermined significance to latent MM is marked by increasing genetic instability, exacerbated in patients with high-risk chromosomal abnormalities. Additionally, the Twist1 protein and miRNA hsa-miR138-5p emerge as potential targets for early diagnosis and treatment. Moreover, the KIAA1191 gene is associated with improved overall and progression-free survival, especially when combined with bortezomib. Risk stratification, including del(17p) and p53 mutation, guides initial therapies such as VRd or Dara-VRd, followed by autologous stem cell transplantation (ASCT). Therefore, treatment personalization, based on biomarkers and risk stratification, is crucial for improving outcomes in MM, ensuring more effective and targeted disease management.