1.What is myeloma? What are the high-risk groups? In myeloma, myeloma plasma cells infiltrate the bone marrow and produce a monoclonal protein, which can be detected in the blood or (and) urine, damaging organs or tissues. Epidemiological studies have shown that the onset of multiple myeloma is preceded by monoclonal immunoglobulinemia of unknown mechanism (MGUS), an asymptomatic disease state. Multiple myeloma occurs most frequently in the elderly (median age 70 years) and can develop at any age, with 15% of diagnosed cases under 60 years of age and 2% under 40 years of age. The incidence of multiple myeloma is twice as high in African-Caribbean as in white people, and is 50% higher in men than in women of all racial groups. There are no known genetic factors or clear environmental risk factors for multiple myeloma. 2. What pathophysiological processes are involved? The pathogenesis of multiple myeloma consists of mutations in genes during the differentiation of B-lymphocytes into plasma cells. In about half of the cases, chromosomal translocations occur, i.e., translocation of the oncogene to the immunoglobulin heavy chain gene (IgH gene translocation) on chromosome 14, resulting in overexpression of the oncogene and uncontrolled cell proliferation. Other pathological features are cells with partial odd trisomies, i.e. chromosomes 3, 5, 7, 9, 11, 15, 19 and 21. the manifestation of these numerous trisomies is called hyperdiploidy. As research has progressed, some genetic mutations, such as mutations in the RAS gene, have also been identified in myeloma. Because myeloma cell growth and survival depend on other cells in the bone marrow, such as fibroblasts, osteoblasts, osteoclasts, stromal cells, and dendritic cells, therapeutic approaches that target the bone marrow microenvironment have progressed. 3. Why does it lead to bone disease and hypercalcemia? The imbalance of bone reconstruction in myeloma patients is caused by increased osteoclast activity and decreased osteoblast function. Myeloma cells promote increased production of osteoclast activators and cytokines that inhibit osteoblast differentiation. Uncontrolled osteolysis can also cause hypercalcemia. 4. Why does it cause renal impairment? In most cases, malignant plasma cells produce abnormal proteins called monoclonal immunoglobulins (mostly IgG or IgA). Multiple myeloma does not usually have abnormal IgM proteins, and their presence often suggests other diseases, such as Walden’s macroglobulinemia. Also plasma cells can produce varying amounts of monoclonal free light chains. Light chains, known as pericardial proteins, can be found in the urine of patients with multiple myeloma and MGUS. About 20% of patients with multiple myeloma have light chains in their serum and urine, while 2% of patients produce neither light chains nor abnormal proteins and are referred to as non-secretory. Light chains are filtered by the glomerulus and reabsorbed by the proximal tubule. When light chain filtration exceeds proximal tubular reabsorption, the light chains precipitate in the distal tubules and form tubular forms, causing tubular obstruction and tubulointerstitial inflammation, leading to acute kidney injury. 90% of renal damage in multiple myeloma is caused by tubular nephropathy. Other causes include amyloid deposition, dehydration, hypercalcemia, hyperviscosemia and the use of nephrotoxic drugs, such as NSAIDs. 5.What are the symptoms of multiple myeloma? Common symptoms include anemia (75%), hypercalcemia (30%), renal impairment (25%), and bone disease (70%). The clinical manifestations of bone disease are painful osteolytic lesions, vertebral comminuted fractures or long bone fractures. Pathologic degenerative fractures of the spine result in spinal cord compression, and plasmacytomas develop in the extramedullary soft tissue in 5% of patients with multiple myeloma. Hypercalcemia, acute renal failure, and spinal cord compression are all emergencies, and prompt diagnosis and treatment are important to reduce long-term organ damage. High levels of abnormal proteins can lead to symptoms of hyperviscosity (headache, rhinorrhea, blurred vision and confusion) and can cause a decrease in humoral immune function leading to recurrent bacterial infections. 30% of confirmed cases are diagnosed by incidental findings of an increased erythrocyte sedimentation rate, total protein or immunoglobulin. Symptoms such as lethargy or back pain are usually non-specific and lead to delayed diagnosis. A recently published report shows that 56% of patients usually present to the hematology department more than 6 months later. One-third of cases are diagnosed in the emergency setting and are not treated regularly, resulting in a poor prognosis for this group of patients (one-year survival rates of 51% and 82%, respectively).