Common manifestations include lytic lesions in bones causing pain. Multiple myeloma is a cancer that develops in the bone marrow, the spongy tissue found in the center of most bones. Cell of origin and genetic alterations in the pathogenesis of multiple. Molecular pathogenesis of multiple myeloma request pdf. Multiple myeloma is predominantly a cancer of terminally differentiated blymphocytes, i. Multiple myeloma is a form of cancer that occurs due to abnormal and uncontrolled growth of plasma cells in the bone marrow. Onlyin one patient was the presence ofa cryo globulinmentioned. Multiple myeloma mm is monoclonal tumor of antibody secreting plasma cells pc in the bone marrow bm, that is often diagnosed by the presence of a typical mspike by serum protein. Multiple myeloma is the second most common type of blood cancer after leukemia. The bone marrow contains stem cells that produce three types. First described in 1848, mm is characterized by a proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraprotein m protein. Multiple myeloma affects slightly more men than women. Plasma cells come from b lymphocytes, and produce antibodies immunoglobulins. Although the pathogenetic mechanisms of disease have been clarified to a large extent, mm remains an incurable disease with low life expectancy.
Multiple myeloma mm, also known as symptomatic plasma cell myeloma, is a plasma cell malignancy. Some people with multiple myeloma, especially those with. A unifying event in the pathogenesis of multiple myeloma is the dysregulated expression of a cyclin d gene, either directly by juxtaposition to an immunoglobulin enhancer, as a result of ectopic expression. Multiple myeloma mm is a neoplasm of postgerminal center, terminally differentiated b cells. The patient handbook focuses on the questions and decisions that a newly diagnosed patient faces. Pathogenesis beyond the cancer clones in multiple myeloma. Myeloma is a cancer of plasma cells that begins in the bone marrow. For example, little is known about the role of the primary events, including cyclin d overexpression and multiple myeloma set domain activity in the early pathogenesis.
Patients endure severe bone pain, pathologic fractures, hypercalcemia, and a markedly decreased quality of life. Malignanat b cell lymphoproliferative disorder of the marrow with plasma cell predominating. In myeloma, the cells grow too much, crowding out normal cells in the bone marrow that make red blood cells, platelets, and other white blood cells. It is characterized by a multifocal proliferation of clonal, longlived plasma cells within the bone marrow. A single mass of myeloma cells is called a solitary plasmacytoma, which is most often found in the bones but can also be found in soft tissue called an extramedullary plasmacytoma.
In this article, the pathophysiology underlying the imbalanced bone remodeling and potential new strategies for the treatment of bone disease in multiple myeloma. This fact sheet is available as a pdf, so it is easy to print out. Today, the cellular and molecular etiology of multiple myeloma as well as the programming of normal b cell development and plasma cell. Multiple myeloma is a hematologic malignancy characterized by the development of a progressive and destructive osteolytic bone disease, associated with severe bone pain, pathological fractures, osteoporosis, hypercalcemia and spinal cord compression. Myelomas are slightly more common in males than in females and can affect any of the marrowcontaining bones, such as the skull, the flat. Ppt multiple myeloma powerpoint presentation free to view.
Molecular pathogenesis of mgus and multiple myeloma. Over the past 4 decades, basic research has provided crucial information regarding the cellular and molecular biology of cancer. In particular, the relevance of cancer microenvironment including both cellular and noncellular elements and the concept of clonal evolution and heterogeneity have emerged as important in cancer pathogenesis, immunologic escape, and resistance to therapy. Multiple myeloma mm is a hematologic tumor characterized by clonal proliferation of neoplastic plasma cells in the bone marrow in association with elevated. N2 multiple myeloma mm is monoclonal tumor of antibody. Jci molecular pathogenesis of multiple myeloma and its. Read a 1page fact sheet that offers an introduction to multiple myeloma. Multiple myeloma represents 2% of all new cancer diagnoses in the united. Multiple myeloma mm is a fatal, malignant bcell neoplasm characterized by uncontrolled, destructive growth of mutated plasma cells within the bone marrow. Ig translocations hyperdiploid vs nonhyperdiploid cyclin d dysregulation other oncogenic events michael kuehl. Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue.
Multiple myeloma early detection, diagnosis, and staging. Pathogenesis paraneoplastic follicular hyperkeratoticspicules. Multiple myeloma dr harpreet singh bhatia dmch, ludhiana,punjab 2. Multiple myeloma mm, one of the most intractable malignancies, is characterized by the infiltration and growth of plasma cells, the most differentiated cells in the bcell lineage, in the bone marrow. For example, little is known about the role of the primary events, including cyclin d overexpression and multiple myeloma set domain activity in the early pathogenesis of the disease. Jan 01, 2005 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. It accounts for 1% of all malignancies and 10% of all haematological malignancies 1,2 and is almost always incurable. Feb 27, 2019 multiple myeloma is a form of cancer that affects bone marrow, the spongy soft tissue that lies within the hollow centre of some bones. Multiple myeloma is a heamatologic malignancy caused by clonal expansion of malignant plasma cells, associated with bone disease and hypercalcaemia as its primary metabolic complication. Understanding the pathogenesis of myeloma bone disease has allowed us to identify novel targets for treating the disease.
Endorgan damage to the kidneys is typically due to light chain cast nephropathy. Ppt multiple myeloma powerpoint presentation free to. Renal involvement is common in multiple myeloma as up to 50% of the patients go on to develop kidney disease at some point during the disease course. In the last five years, significant advances have been made in the understanding of the pathogenesis, natural history, and prognosis of mgus and smm. Myeloma plasma b cells also express cxcr4 receptors for sdf1. Half of these patients recover kidney function while the rest of them develop chronic kidney dysfunction. Multiple myeloma genetic and rare diseases information. The precise etiology of mm has not yet been established. 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. The pathogenesis of the bone disease of multiple myeloma. N2 multiple myeloma mm is monoclonal tumor of antibody secreting plasma cells pc in the bone marrow bm, that is often diagnosed by the presence of a typical mspike by serum protein electrophoresis spep, or by free light chains in the urine. In particular, the relevance of cancer microenvironment including both cellular and noncellular elements and the concept of clonal evolution and heterogeneity have emerged as important in cancer pathogenesis. View a short video led by an asco expert and patient advocate that provides basic information and areas of research related to multiple myeloma.
Learn more about the symptoms, causes, diagnosis, risk factors, and treatment of multiple myeloma. During the course of multiple myeloma most patients exhibit a tendency to bleed. Like their discoveries, we have learned much about multiple myeloma from studying the normal processes of plasma cell differentiation and vice versa. Although it may be an early manifestation, the incidence of abnormal bleeding is greater in the more advanced phases. Pathogenesis and treatments cliodhna browne tsmj issue 10 2009 30 abstract multiple myeloma is a clonal b cell malignancy involving terminally differentiated plasma cells. It is characterized by a multifocal proliferation of clonal, longlived plasma cells within the bone marrow bm and associated skeletal destruction, serum monoclonal gammopathy, immune suppression, and endorgan sequelae.
Despite this progress, several questions of critical importance remain to be addressed for the understanding of the pathogenesis of multiple myeloma. Multiple myeloma early detection, diagnosis, and staging 1. 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. The molecular mechanisms associated with disease progression in mm are dependent on the interaction between mm cells and the bone marrow microenvironment. The plasma cells proliferate in the bone marrow and often. 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. Common manifestations include lytic lesions in bones causing pain, andor fractures, renal insufficiency, hypercalcemia, anemia, and recurrent infections. It is characterized by a multifocal proliferation of clonal, long lived. Myeloma is a cancer of the plasma cells in the bone marrow. Cell of origin and genetic alterations in the pathogenesis.
Request pdf on feb 1, 2009, wm kuehl and others published molecular pathogenesis of mgus and multiple myeloma find, read and cite all the research you need on researchgate. Multiple myeloma mm is characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin. In the last five years, significant advances have been made in the understanding of the pathogenesis. Myeloma is synonymous with multiple myeloma and plasma cell myeloma. Multiple myeloma mm is the most frequent cancer to involve the skeleton with 8090% of patients developing bone lesions during their disease course. Several genetic mechanisms underlying the pathogenesis of multiple myeloma have been elucidated in the past decade. Despite the introduction of novel therapeutic agents, including proteasome inhibitors and immunomodulatory drugs, the prognosis of patients with mm is still worse than that of most. 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. 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. Jul 14, 2017 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.
Multiple myeloma is the secondmost prevalent blood cancer 10% after nonhodgkins lymphoma. Cell of origin and genetic alterations in the pathogenesis of. It will help you learn medical terms and concepts you may not have encountered before. Mullighan new molecular insights into peripheral t cell lymphomas stefano a. In the disease state, bone healing is limited owing to increased osteoclastic and decreased. This is a pdf file of an unedited manuscript that has been. Mar 19, 2020 multiple myeloma, malignant proliferation of cells within the bone marrow that usually occurs during middle age or later and increases in occurrence with age. Leif bergsagel2 1genetics branch, center for cancer research, national cancer institute, bethesda.
Myeloma bone lesions are purely osteolytic and are associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. The imf is dedicated to improving the quality of life of myeloma. Molecular genetics of bprecursor acute lymphoblastic leukemia charles g. The bone marrow produces red blood cells, which carry oxygen throughout the body. Interpretation of cytogenetic results in multiple myeloma for. Molecular pathogenesis of multiple myeloma sciencedirect. It is characterised by a clonal population of bone marrow plasma cells which secrete a monoclonal. Molecular pathogenesis of multiple myeloma and its premalignant. A unifying event in the pathogenesis of multiple myeloma is the dysregulated expression of a cyclin d gene, either directly by juxtaposition to an immunoglobulin enhancer, as a result of ectopic expression of a maf family transcription factor, or indirectly by as yet unidentified mechanisms.
Recently the biologic mechanism involved in the imbalance between osteoclast activation and osteoblast inhibition induced by multiple myeloma cells has begun to be clarified. Multiple myeloma hematology and oncology merck manuals. Multiple myeloma is a fatal hematologic malignancy associated with clonal expansion of malignant plasma cells within the bone marrow and the development of a destructive osteolytic bone disease. A free powerpoint ppt presentation displayed as a flash slide show on id. Abnormal antibody fragments are produced in multiple myeloma and are deposited in various organs, such as the kidneys. Myeloma is called multiple because it frequently involves multiple areas in the body. There are three major forms of renal damage in patients with multiple myeloma. Monoclonal gammopathy of undetermined significance mgus including immunoglobulin light chain only mgus is an age dependent premalignant tumor that is present in about 4% of caucasian.
Multiple myeloma, malignant proliferation of cells within the bone marrow that usually occurs during middle age or later and increases in occurrence with age. The imfs reach extends to more than 525,000 members in 140 countries worldwide. Despite the incredible progress made and knowledge gained, over,000 new cases of multiple myeloma occur every year worldwide, including over 30,000 cases in the us alone. Jan 11, 2016 myeloma classification monoclonal gammopathy of undetermined significance serum mprotein 3 gdl andor bone marrow plasma cells. Pdf multiple myeloma is divided into two distinct genetic subtypes based on chromosome content. Failure of apoptosis, angiogenesis and bone marrow interaction with malignant cells. Molecular pathogenesis of multiple myeloma and its premalignant precursor w. In support of a role for runx2 in the pathophysiology of myeloma bone disease. The causes of renal involvement in multiple myeloma are multiple and diverse.
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. Multiple myeloma mm, a cancer of terminally differentiated plasma cells, is emblematic of the impact of cancer microenvironment and the role. We hope that the information will be helpful to both healthcare professionals and patients. Obd or osteopenia is one of the defining features of multiple myeloma mm. Multiple myeloma mm is monoclonal tumor of antibody secreting plasma cells pc in the bone marrow bm, that is often diagnosed by the presence of a typical mspike by serum protein electrophoresis spep, or by free light chains in the urine. Mm is characterized by several cytogenetic abnormalities that occur at various time points in. In particular, the presence of two distinct karyotypic patterns, that identify. Oct 30, 2015 the interpretation of cytogenetic abnormalities in multiple myeloma mm is often a challenging task. Roles have been suggested for a variety of factors, including genetic causes. In 2015, an estimated 28,850 new cases of multiple myeloma were. Multiple myeloma annals of internal medicine american.
Multiple myeloma mm is a plasma cell dyscrasia characterized by malignant proliferation of monoclonal plasma cells in the bone marrow. Multiple myeloma is a form of cancer that affects bone marrow, the spongy soft tissue that lies within the hollow centre of some bones. Despite the incredible progress made and knowledge gained, over,000 new cases of multiple myeloma. Multiple myeloma mm is an agedependent monoclonal tumor of bm plasma cells pcs. Herein, we provide an insight into the underlying pathogenesis of bone disease and discuss possible directions for future studies. Osteolytic lesions develop in nearly 90% of patients with mm. Pathogenesis of monoclonal gammopathy of undetermined. Myeloma, also called multiple myeloma, is a cancer of the plasma cells. Molecular pathogenesis of multiple myeloma springerlink. The severity of bleeding varies from petechiae to exsanguination. Myeloma bone disease is responsible for some of the most devastating complications of the disease.
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