Multiple myeloma mm is a b cell malignancy resulting in osteolytic lesions and fractures. Multiple myeloma is one of the hematological illnesses that we see in addition to lymphomas and leukemias in nonhodgkins lymphoma, as well as in hodgkins lymphoma. Multiple myeloma mm is a monoclonal tumor of antibodysecreting 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. 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. Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. 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. In particular, the presence of two distinct karyotypic patterns, that identify. Once reversible factors such as hypercalcemia have been corrected, the most common cause of severe renal failure in these patients is a tubulointerstitial pathology that results from the very high circulating concentrations of monoclonal immunoglobulin free light chains.
The bone marrow niche in the pathogenesis of multiple myeloma. Myelomas are slightly more common in males than in females and can affect any of the marrowcontaining bones, such as the skull, the flat. Multiple myeloma is the malignant counterpart of longlived plasma cells with a strong tropism for bone and bone marrow. Keywords multiple myeloma, mgus, plasma cell development, myeloma cancer stem cell, bone marrow microenvironment, myeloma oncogenomics. 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. In recent years, the therapeutic options to treat mm have rapidly expanded leading to. Pdf multiple myeloma is divided into two distinct genetic subtypes based on chromosome content. 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. Lenalidomide is an immunomodulatory drug with potent antitumor, antiangiogenic, immunomodulatory, and proapoptotic activity in mm. 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 cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. The pathogenesis of the bone disease of multiple myeloma. Several genetic mechanisms underlying the pathogenesis of multiple myeloma have been elucidated in the past decade.
Jan 12, 2018 multiple myeloma mm is a plasma cell dyscrasia characterized by malignant proliferation of monoclonal plasma cells in the bone marrow. 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. Jci studies on the pathogenesis of an immune defect in. Multiple myeloma mm is a malignancy of plasma cells which represents about 2% of all new cancer cases in the united kingdom.
Multiple myeloma is an incurable disease and, little is known about the genetic and molecular mechanism governing its pathogenesis 3. Plasma cells are a type of white blood cell found in bone marrow, which is the soft tissue inside most of your bones that produces. Multiple myeloma is a form of cancer that affects bone marrow, the spongy soft tissue that lies within the hollow centre of some bones. Micrornas regulate critical genes associated with multiple. Pathogenesis beyond the cancer clones in multiple myeloma. Multiple myeloma mm, a cancer of terminally differentiated plasma cells, is emblematic of the impact of cancer microenvironment and the role. Studies on the pathogenesis of an immune defect in multiple myeloma teresa paglieroni and. Multiple myeloma hematology and oncology merck manuals.
Despite this progress, several questions of critical importance remain to be addressed for the understanding of the pathogenesis of multiple myeloma. Multiple myeloma mm is a neoplasm of postgerminal center, terminally differentiated b cells. The pathogenesis and diagnosis of acute kidney injury in. Multiple myeloma mm, which accounts for approximately 10% of all haematological malignancies, is a clonal, late b cell malignancy in which plasma cells pc accumulate in the bone marrow bm. The b one marrow niche in the p athogenesis of m u ltip le m yeloma. Pathogenesis and treatment of renal failure in multiple myeloma. Current advances have led to increased survival, 3,4 although this is still much shorter than for other mature bcell malignancies, such as. Renal failure is a frequent complication in patients with multiple myeloma mm that causes significant morbidity. Pathogenesis and treatment of renal failure in multiple.
Plasma cells come from b lymphocytes, and produce antibodies immunoglobulins. Failure of apoptosis, angiogenesis and bone marrow interaction with malignant cells. Leif bergsagel 2 1 genetics branch, center for cancer research, national cancer institute, bethesda, maryland, usa. The basis of the pathogenesis of myelomarelated bone disease is the uncoupling of the boneremodeling process. It is now known that myeloma is a progressive disease preceded by an asymptomatic stage called mgus 19, 20 often followed by an intermediate stage referred to as smoldering multiple myeloma smm, prior to symptomatic newly diagnosed multiple. Multiple myeloma is a cancer that forms in a type of white blood cell called a plasma cell. Myeloma, also called multiple myeloma, is a cancer of the plasma cells. 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.
Plasma cells help you fight infections by making antibodies that recognize and attack germs. 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. The bone marrow contains stem cells that produce three types. In germany there are around 6500 new cases of multiple myeloma each year and it is the third most commonly occurring disease of. Multiple myeloma accounts for around 1% of all cancers worldwide and 1015% of all hematological neoplasms. Jul 11, 2016 multiple myeloma accounts for around 1% of all cancers worldwide and 1015% of all hematological neoplasms. Among other plasma cell dyscrasias, such as waldenstroms macroglobulinaemia and primary amyloidosis, multiple myeloma is the second most frequent haematological malignancy with an ageadjusted incidence of six per 100 000 per year in the usa and europe.
Multiple myeloma represents 2% of all new cancer diagnoses in the united. Multiple myeloma dr harpreet singh bhatia dmch, ludhiana,punjab 2. 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. In the disease state, bone healing is limited owing to increased osteoclastic and decreased osteoblastic activity, as well as an mm. Jan 11, 2016 myeloma classification monoclonal gammopathy of undetermined significance serum mprotein 3 gdl andor bone marrow plasma cells. 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. In the last five years, significant advances have been made in the understanding of the pathogenesis, natural history, and prognosis of mgus and smm. 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. Currently, there is no single standard therapy, with choice of treatment dependent on individual patient factors. The molecular mechanisms associated with disease progression in mm are dependent on the interaction between mm cells and the bone marrow microenvironment. Studies onthe pathogenesis ofan immunedefect in multiple myeloma teresapaglieroni and malcolmr. Cell of origin and genetic alterations in the pathogenesis.
In malaysia, more than 50% of myeloma patients were diagnosed at stage iv of the disease based on clinical staging system and it is more prevalent in men than women 2. In the last five years, significant advances have been made in the understanding of the pathogenesis, natural history, and. Jci molecular pathogenesis of multiple myeloma and its. Multiple myeloma mm is a relatively common and incurable hematological malignancy. Molecular pathogenesis of multiple myeloma springerlink. Molecular genetics of bprecursor acute lymphoblastic leukemia charles g. Multiple myeloma mm is characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin. Pathogenesis and treatments cliodhna browne tsmj issue 10 2009 30 abstract multiple myeloma is a clonal b cell malignancy involving terminally differentiated plasma cells.
Multiple myeloma is predominantly a cancer of terminally differentiated blymphocytes, i. Multiple myeloma is a type of cancer that affects plasma cells. First described in 1848, mm is characterized by a proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraprotein m protein. Micrornas regulate critical genes associated with multiple myeloma pathogenesis flavia pichiorri, sungsuk suh, marco ladetto, michael kuehl, tiziana palumbo, daniela drandi.
Progress in understanding the biology of multiple myeloma mm, a plasma cell malignancy, has been slow. Aug 16, 2018 multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. Molecular pathogenesis of multiple myeloma request pdf. Multiple myeloma mm is a plasma cell dyscrasia characterized by malignant proliferation of monoclonal plasma cells in the bone marrow. Mackenzie from the department of internal medicine, section of hematology and oncology, university of california at davis school ofmedicine, davis, california 95616 abstract thereduced capacity ofpatients with. Multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. Leif bergsagel2 1genetics branch, center for cancer research, national cancer institute, bethesda, maryland, usa. Common manifestations include lytic lesions in bones causing pain, andor fractures, renal insufficiency, hypercalcemia, anemia, and recurrent infections. Molecular pathogenesis of multiple myeloma sciencedirect. Multiple myeloma is the second most common type of blood cancer after leukemia.
Some early cancers may have signs and symptoms that can be noticed, but that is not always the case. Multiple myeloma early detection, diagnosis, and staging. Multiple myeloma mm is a bcell malignancy characterized by the clonal proliferation of malignant plasma cells in the bone marrow. Mar 22, 2016 multiple myeloma mm is a b cell malignancy resulting in osteolytic lesions and fractures. Renal failure remains a principal cause of morbidity for patients with multiple myeloma. Malignanat b cell lymphoproliferative disorder of the marrow with plasma cell predominating. Studies on the pathogenesis of immune defect in multiple. Mm is preceded by an ageprogressive premalignant condition termed. Over the past 4 decades, basic research has provided crucial information regarding the cellular and molecular biology of cancer.
Multiple myeloma mm is a hematologic tumor characterized by clonal proliferation of neoplastic plasma cells in the bone marrow in association with elevated. 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. In the majority of cases, renal impairment is caused by the accumulation and. Multiple myeloma mm is the most frequent cancer to involve the skeleton with up to 90% of patients with mm developing bone lesions. Multiple myeloma early detection, diagnosis, and staging 1.
Molecular pathogenesis of multiple myeloma and its premalignant precursor w. 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. Pcaf socs1 tumor suppressor gene mgus plasma cells m ultiple myeloma mm is a bcell neoplasm characterized. Whether you or a loved one are worried about developing multiple myeloma, have just been diagnosed, are going through treatment, or are trying to stay well after treatment, this detailed guide can help you find the answers you need. Cell of origin and genetic alterations in the pathogenesis of multiple. A report from the uk in the early 1970s found that patients with multiple myeloma and severe aki had a median survival of 2 months compared with 3 years for patients presenting with moderate renal impairment. The plasma cells proliferate in the bone marrow and often results in extensive skeletal destruction with osteolytic lesions, osteopenia, andor pathologic fractures.
Myelomas are slightly more common in males than in females and can affect any of the marrowcontaining bones, such as. In germany there are around 6500 new cases of multiple myeloma each year and it is the third most commonly occurring disease of the blood after leukemia and nonhodgkin lymphoma. Feb 04, 2020 mutated lymphopoiesis and b cell oligoclonality can precede the pathogenesis of multiple myeloma and persist in patients with negative measurable residual disease. Immunoglobulin synthesis and mixed leukocyte responses by normal peripheral blood lymphocytes could be suppressed by myeloma lymphocytes.
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