Myeloma is a cancer of the plasma cell, a type of white blood cell that is part of the immune system. To aid preclinical development of novel therapeutics for myeloma, an in vivo model which recapitulates the human condition is required. Aug 3, 20 my mother had multiple myeloma for over 18 years. N2 multiple myeloma is divided into two distinct genetic subtypes based on chromosome content. 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.
Multiple myeloma side effect management people are sometimes afraid if they report a certain effect that theyll be taken off the clinical trial or the drug or whatever that theyre on. Sandy hirsch charlotte multiple myeloma support group. Hyperdiploid myeloma is characterized by multiple trisomies of chromosomes 3, 5, 7, 9 11, 15, 19 and 21. Plasma cells develop from one type of white blood cell called b lymphocytes and are an important part of the immune system. American roentgen ray society images of multiple myeloma all images xrays echo and ultrasound ct images mri. Failure of apoptosis, angiogenesis and bone marrow. Recognition of potential adverse cytogenetic and genomic abnormalities has led to identification of newer targets.
American roentgen ray society images of multiple myeloma all images x. Hyperdiploid myeloma is characterized by multiple trisomies of chromosomes 3, 5, 7, 9 11, 15, 19 and. Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma.
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. Highquality 3d animation films about the mechanism of disease and the mechanism of action provide internal target groups with exact. Pathogenesis and treatment of myeloma bone disease youtube. Some early cancers may have signs and symptoms that can be noticed, but that is not always the case. Monoclonal gammopathy of undetermined significance mgus consistently precedes multiple myeloma. Molecular pathogenesis of multiple myeloma and its. B2 activation has been implicated in the pathogenesis of multiple myeloma, a. In the united states, multiple myeloma myeloma, plasma cell myeloma is the third most common hematologic malignancy after lymphoma and leukemia 1 but the 14th most common malignancy overall.
Multiple myeloma mm is an agedependent monoclonal tumor of bm plasma cells pcs. Pathogenesis beyond the cancer clones in multiple myeloma ncbi. As the covid19 respiratory virus spreads around the world, the international myeloma foundation imf continues to be here for you. It is characterised by a clonal population of bone marrow plasma cells which secrete a monoclonal. Multiple myeloma is the secondmost prevalent blood cancer 10% after nonhodgkins lymphoma. Jul 26, 2016 multiple myeloma currently is an incurable blood cancer and relapse is inevitable for almost all patients. 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. Multiple myeloma is divided into two distinct genetic subtypes based on chromosome content. Multiple myeloma mm is a plasma cell dyscrasia characterized by malignant proliferation of monoclonal plasma cells in the bone marrow.
Understanding multiple myeloma pathogenesis in the bone. 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. Jan 11, 2016 myeloma classification monoclonal gammopathy of undetermined significance serum mprotein 3 gdl andor bone marrow plasma cells. The molecular mechanisms associated with disease progression in mm are dependent on the interaction between mm cells and the bone marrow microenvironment.
Acquired genetic mutations within myeloma cells and their interaction with bone marrow. Bone disease remains one of the most serious aspects of multiple. Igm lt 1 igd lt1 ige lt1 29 pathogenesis of multiple myeloma. Multiple myeloma affects slightly more men than women.
Mm pathogenesis can be further evaluated by crossing mice with. Multiple myeloma research foundation mmrf 1866603mmct founded in 1998, the mmrf is a nonprofit organization that provides facts, information, and resources about multiple. Multiple myeloma mm is a cancer of antibodyproducing plasma cells. Expecting to get better, some actually wind up getting worse. First described in 1848, mm is characterized by a proliferation of malignant plasma cells and a subsequent overabundance of monoclonal paraprotein m protein. Ppt multiple myeloma mm powerpoint presentation free. Multiple myeloma is classified by stage 1, 2, or 3. Complications may include amyloidosis the cause of multiple myeloma is unknown. Over the past 4 decades, basic research has provided crucial information regarding the cellular and molecular biology of cancer. It is characterised by a clonal population of bone marrow plasma cells which secrete a monoclonal paraprotein or an immunoglobulin free light chain flc figure 1a, b. Imaging studies and the development of multiple myeloma. Carfilzomib in treatment patients under 65 years with high. 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.
An important feature of such a model is the interaction of myeloma cells with the bone marrow microenvironment, as this interaction modulates tumour activity and protects against druginduced apoptosis. This cartoon is a schematic representation of the clonal evolution of multiple. Little is known about the genetic and molecular mechanisms governing the pathogenesis of multiple myeloma. Elevated il17 produced by th17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma.
Mm cells are similar to longlived, postgerminal center postgc pcs, and are characterized by strong bm dependence, extensive somatic hypermutation shm of ig genes, and absence of igm expression in all but 1% of tumors. See more ideas about multiple myeloma and bone marrow. May 26, 2020 june 29, 2017 a new type of therapeutic could greatly reduce bone disease in patients with the bone cancer, multiple myeloma. This means its the most advanced stage of this type of rare cancer. Updated diagnostic criteria and staging system for.
Multiple myeloma can be caused by genetic mutations and chromosomal aberrations. Leveraging her past experience as a leader of a major pharmaceutical company. It is a highly manageable disease that has seen rapid medical advancements in the past few years. Murine models of human multiple myeloma mm are key tools for the study. Multiple myeloma early detection, diagnosis, and staging 1. Mm cells are similar to longlived, postgerminal center postgc pcs, and are characterized by strong bm.
Osteolytic bone lesions are commonly observed in patients with active multiple myeloma. Highthroughput sequencing of mm patient samples has identified novel driver mutations beyond classical cancer mutations nras, kras, and tp53. 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 epidemiology and patient geographic distribution in canada. Multiple myeloma mm, also known as plasma cell myeloma and simple myeloma, is a cancer. Myeloma is a cancer of plasma cells that begins in the bone marrow. T1 understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Molecular pathogenesis of multiple myeloma request pdf. Characterization of a novel mouse model of multiple. Recurring chromosomal translocations in multiple myeloma cyclin d induces growth mmset growth factor cmaf transcription factor cmyc growthapoptosis mum transcription factor.
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. No myeloma defining events smoldering myeloma m protein. A systematic analysis for the global burden of disease study 2016. Pathogenesis beyond the cancer clones in multiple myeloma. Jci molecular pathogenesis of multiple myeloma and its. Ppt multiple myeloma mm powerpoint presentation free to. Multiple myeloma is part of the broad group of diseases called hematological malignancies and is also known as plasma cell myeloma, myelomatosis, or kahler disease. Characterization of a novel mouse model of multiple myeloma.
Multiple myeloma mm is a relatively common and incurable hematological malignancy. 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. Common manifestations include lytic lesions in bones causing pain. Multiple myeloma currently is an incurable blood cancer and relapse is inevitable for almost all patients. Interaction of malignant plasma cells with the bone marrow microenvironment plays a key role in the pathogenesis of myeloma. Multiple myeloma is a cancer that develops in bone, causing. Multiple myeloma hematology and oncology merck manuals. Weve all heard the horror stories about hospital risks after surgery. Her doctors called her their poster child because she survived so long with this horrible disease. Multiple myeloma from bench to bedside, and back wiley online. Research foundation homepage multiple myeloma research.
Molecular pathogenesis of multiple myeloma springerlink. As it progresses, bone pain, bleeding, frequent infections, and anemia may occur. Multiple myeloma mm, a cancer of terminally differentiated plasma cells, is emblematic of the impact of cancer microenvironment and the role of clonal evolution. Multiple myeloma mm, also known as symptomatic plasma cell myeloma, is a plasma cell malignancy. This video provides information regarding relapsed and refractory multiple myeloma and. Based on karyotype, mm is classified as nonhyperdiploid and hyperdiploid, with the latter accounting for 50% to 60% of cases and characterized by trisomies in odd chromosomes 3, 5, 7, 9, 11, 15, 19, and 21. 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 the most frequent cancer to involve the skeleton with 8090% of patients developing bone lesions during their disease course. The greatest risk period for the occurrence of infection is in the initial few months after the start of chemotherapy. Times new roman arial steinkraus multiple myeloma mm case study multiple myeloma case study. About the multiple myeloma research foundation shortly after being diagnosed with multiple myeloma, kathy giusti and her sister karen andrews, a successful corporate attorney, founded the mmrf in 1998 with the hope of one day finding a cure for this fatal blood cancer. Igg kappa 30 or lambda 18 iga kappa 10 or lambda 6 free kappa or lambda 15 to 20 bencejones proteins.
New approaches to molecular imaging of multiple myeloma. Multiple myeloma is a mature plasma cell neoplastic proliferative disease. Failure of apoptosis, angiogenesis and bone marrow interaction with malignant cells all contribute to the pathogenesis of the disease. Ig translocations hyperdiploid vs nonhyperdiploid cyclin d dysregulation other oncogenic events michael kuehl. Common manifestations include lytic lesions in bones causing pain, andor fractures, renal insufficiency, hypercalcemia, anemia, and recurrent infections. When in reality most of the times, that kind of a drug is that kind of a side effect is something thats expected.
Cell of origin and genetic alterations in the pathogenesis of multiple. Multiple myeloma is a cancer of your plasma cells, a type of white blood cell present in your bone marrow. There is no cure for multiple myeloma, but treatments are available that slow its progression. Multiple myeloma is caused by clonal expansion of malignant plasma cells within the bone marrow. Based on ig isotypes with frequency parallel to normal serum percentages.
1580 696 1115 34 436 1595 639 291 579 1499 400 1360 935 1252 1476 228 1020 607 308 589 870 1463 5 270 1578 443 742 1123 705 62 488 1475 138 932 1425 405 688 979 1290 1223 1301 430 1499 116 40