B diagram of stages of myeloma progressing from a normal plasma cell to monoclonal gammopathy of undetermined significance mgus. Subclonal evolution in disease progression from mgussmm. Epidemiology and pathophysiology multiple myeloma accounts for 1. Pathogenesis beyond the cancer clones in multiple myeloma. Since multiple myeloma has a median survival of only 3 to 4 years, 2, 3 predicting and preventing the progression of mgus and smm to myeloma is of great importance. Herein, we provide an insight into the underlying pathogenesis of bone disease and discuss possible directions for future studies. Scribd is the worlds largest social reading and publishing site. In 2015, an estimated 28,850 new cases of multiple myeloma. The major features of myeloma result from the abnormal accumulation of myeloma cells within the bone marrow, causing. Multiple myeloma dr harpreet singh bhatia dmch, ludhiana,punjab 2.
Multiple myeloma epidemiology and patient geographic distribution in canada. Multiple myeloma is a form of cancer that affects bone marrow, the spongy soft tissue that lies within the hollow centre of some bones. There are three major forms of renal damage in patients with multiple myeloma. Pathophysiology and diagnosis of multiple myeloma jatin shah, md, explains that there is no clear reason for why patients develop multiple myeloma, and so theres no clear risk factor. Virtually every case of mm is preceded by a premalignant pc tumor called monoclonal gammopathy of undetermined significance mgus 6, 7 that, like mm. Several genetic mechanisms underlying the pathogenesis of multiple myeloma have been elucidated in the past decade. Malignanat b cell lymphoproliferative disorder of the marrow with plasma cell predominating. Bone destruction in mm results from increased osteoclast formation and activity that occur in close proximity to myeloma cells. The median age at diagnosis of multiple myeloma is 69 years, with threequarters of patients being diagnosed above the. Molecular pathogenesis of multiple myeloma request pdf. Myeloma is a cancer of the plasma cells in the bone marrow. Multiple myeloma mm is a malignancy of plasma cells which represents about 2% of all new cancer cases in the united kingdom. In the disease state, bone healing is limited owing to increased osteoclastic and decreased.
Multiple myeloma is the second most common type of blood cancer after leukemia. Multiple myeloma is a cancer that develops in the bone marrow, the spongy tissue found in the center of most bones. Plasma cells come from b lymphocytes, and produce antibodies immunoglobulins. Multiple myeloma mm is a fatal, malignant bcell neoplasm characterized by uncontrolled, destructive growth of mutated plasma cells within the bone marrow.
Multiple myeloma mm is a largely incurable haematological malignancy defined by the clonal proliferation of malignant plasma cells pcs within the bone marrow. Multiple myeloma mm is a plasma cell malignancy in which monoclonal plasma cells proliferate in bone marrow, resulting in an overabundance of monoclonal paraprotein m protein, destruction of bone, and displacement of other hematopoietic cell lines. N2 multiple myeloma mm is monoclonal tumor of antibody. For understanding of the pathophysiology of multiple myeloma, features of the malignant clone and changes induced by the bonemarrow microenvironment are equally important. Multiple myeloma mm is a debilitating malignancy that is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance mgus to plasma cell leukemia. Multiple myeloma early detection, diagnosis, and staging. Complications may include amyloidosis the cause of multiple myeloma. Bone destruction is a hallmark of multiple myeloma mm. Some early cancers may have signs and symptoms that can be noticed, but that is not always the case. Multiple myeloma mm is a b cell malignancy resulting in osteolytic lesions and fractures. Minimal residual disease in multiple myeloma multiple myeloma pathophysiology and epidemiology multiple myeloma mm is a plasma cell malignancy in which abnormal, clonal plasma cells proliferate and accumulate within the bone marrow. Pathogenesis multiple myeloma is a malignancy of plasma b cells caused by alterations to genetic material following b cell activation in the germinal centres of secondary lymphoid organs.
The disease is rare in individuals younger than 40 years, with a median age of diagnosis of 60 years. Multiple myeloma mm is a plasma cell dyscrasia characterized by malignant proliferation of monoclonal plasma cells in the bone marrow. In the last five years, significant advances have been made in the understanding of the pathogenesis. Multiple myeloma early detection, diagnosis, and staging 1. Multiple myeloma mm is a plasma cell malignancy characterized by a high capacity to induce osteolytic bone lesions. Molecular pathogenesis of multiple myeloma and its premalignant precursor w. Multiple myeloma is a form of cancer that affects bone marrow, the. Usually, the bones of the hands, feet, and lower parts of the arms and legs are not affected, preserving the function of these critical areas. New insights into the pathophysiology of multiple myeloma. Multiple myeloma mm, a cancer of terminally differentiated plasma cells, is emblematic of the impact of cancer microenvironment and the role. In a large series of renal transplant patients who developed ptld, the overall incidence of multiple myeloma was 0.
Multiple myeloma is a monoclonal tumor of plasma cells, and its development is preceded by a premalignant tumor with which it shares genetic. Destruction and invasion of bone and surrounding areas of bone marrow involvement. The diagnosis can be established by bone marrow aspiration, which documents prominent collections of. The imfs patient handbook is designed to help you to understand multiple myeloma which we refer to simply as myeloma. The bone marrow niche in the pathogenesis of multiple myeloma a role for wnt signaling and adrenomedullin the bone marrow niche in the pathogenesis of multiple myeloma a role for wnt. Disruption of normal bone marrow function reflected by anemia andor low white counts or platelet counts. The bone marrow produces red blood cells, which carry oxygen throughout the body. Pdf multiple myeloma is divided into two distinct genetic subtypes based on chromosome content. Multiple myeloma is characterized by either a focal or a diffuse abnormal overgrowth of plasma cells, occurring predominantly in the 40 to 70year age group. Leif bergsagel2 1genetics branch, center for cancer research, national cancer institute, bethesda. Learn more about the symptoms, causes, diagnosis, risk factors, and treatment of multiple myeloma. Multiple myeloma mm is the most frequent cancer to involve the skeleton with 8090% of patients developing bone lesions during their disease course. Pathogenesis of monoclonal gammopathy of undetermined. Lung cancer\\u2014nonsmall cell localregionalsmall.
Multiple myeloma mm, also known as plasma cell myeloma and simple myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Myeloma most often grows in the marrow within the bones of the spine, skull, pelvis, rib cage, shoulders, and hips. Endorgan damage to the kidneys is typically due to light chain cast nephropathy. In particular, the presence of two distinct karyotypic patterns, that identify two patient groups and drive different pathogenetic and prognostic paths in the development of myeloma. Osteolytic lesions result from increased bone resorption due to stimulation of osteoclast formation and activity that occurs in close proximity to myeloma.
Pdf myeloma bone disease mbd is a devastating complication of multiple myeloma. Molecular pathogenesis of multiple myeloma and its premalignant. Bone destruction and lack of bone formation are main factors in the. The bone marrow niche in the pathogenesis of multiple. As it progresses, bone pain, bleeding, frequent infections, and anemia may occur. Multiple myeloma mm is a bcell malignancy characterized by the clonal proliferation of malignant plasma cells in the bone marrow. Molecular pathogenesis of multiple myeloma sciencedirect. Multiple myeloma mm, the second most common hematological malignancy in the united states, presently is a mostly incurable disease, with an incidence of about 20,000 cases per year and. We hope that the information will be helpful to both healthcare professionals and patients. Myeloma is called multiple because it frequently involves multiple areas in the. Cell of origin and genetic alterations in the pathogenesis of multiple. Multiple myeloma mm is a malignancy of plasma cells that leads to anemia, kidney failure.
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