Multiple Myeloma: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.Myeloma Proteins: Abnormal immunoglobulins characteristic of MULTIPLE MYELOMA.Boronic Acids: Inorganic or organic compounds that contain the basic structure RB(OH)2.PyrazinesThalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.Plasma Cells: Specialized forms of antibody-producing B-LYMPHOCYTES. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. (Rosen et al., Dictionary of Immunology, 1989, p169 & Abbas et al., Cellular and Molecular Immunology, 2d ed, p20)Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.Paraproteinemias: A group of related diseases characterized by an unbalanced or disproportionate proliferation of immunoglobulin-producing cells, usually from a single clone. These cells frequently secrete a structurally homogeneous immunoglobulin (M-component) and/or an abnormal immunoglobulin.Monoclonal Gammopathy of Undetermined Significance: Conditions characterized by the presence of M protein (Monoclonal protein) in serum or urine without clinical manifestations of plasma cell dyscrasia.Leukemia, Plasma Cell: A rare, aggressive variant of MULTIPLE MYELOMA characterized by the circulation of excessive PLASMA CELLS in the peripheral blood. It can be a primary manifestation of multiple myeloma or develop as a terminal complication during the disease.Plasmacytoma: Any discrete, presumably solitary, mass of neoplastic PLASMA CELLS either in BONE MARROW or various extramedullary sites.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Transplantation, Autologous: Transplantation of an individual's own tissue from one site to another site.Syndecan-1: A syndecan that interacts with EXTRACELLULAR MATRIX PROTEINS and plays a role CELL PROLIFERATION and CELL MIGRATION.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Cell Line, Tumor: A cell line derived from cultured tumor cells.Bence Jones Protein: An abnormal protein with unusual thermosolubility characteristics that is found in the urine of patients with MULTIPLE MYELOMA.Paraproteins: Abnormal immunoglobulins synthesized by atypical cells of the MONONUCLEAR PHAGOCYTE SYSTEM. Paraproteins containing only light chains lead to Bence Jones paraproteinemia, while the presence of only atypical heavy chains leads to heavy chain disease. Most of the paraproteins show themselves as an M-component (monoclonal gammopathy) in electrophoresis. Diclonal and polyclonal paraproteins are much less frequently encountered.Immunoglobulin Light Chains: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.Antineoplastic Combined Chemotherapy Protocols: The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.Proteasome Inhibitors: Compounds that inhibit the function or proteolytic action of the PROTEASOME.Hematopoietic Stem Cell Transplantation: Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium.Bone Diseases: Diseases of BONES.Interleukin-6: A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.Waldenstrom Macroglobulinemia: A lymphoproliferative disorder characterized by pleomorphic B-LYMPHOCYTES including PLASMA CELLS, with increased levels of monoclonal serum IMMUNOGLOBULIN M. There is lymphoplasmacytic cells infiltration into bone marrow and often other tissues, also known as lymphoplasmacytic lymphoma. Clinical features include ANEMIA; HEMORRHAGES; and hyperviscosity.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Chromosomes, Human, Pair 14: A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Immunoglobulin kappa-Chains: One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.Diphosphonates: Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.Vincristine: An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.)Syndecans: A family of transmembrane glycoproteins that contain a short cytoplasmic domain, a single-span transmembrane domain, and an extracellular domain with heparin sulfate and CHONDROITIN SULFATE chains. Syndecans interact with a variety of heparin-binding INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS and may play a role in modulating cellular signaling during EMBRYONIC DEVELOPMENT, tumorigenesis, and angiogenesis.Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Maintenance Chemotherapy: Treatment designed to help prevent a relapse of a disease following the successful primary treatments (INDUCTION CHEMOTHERAPY and CONSOLIDATION CHEMOTHERAPY) with a long-term low-dose drug therapy.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Immunoglobulin lambda-Chains: One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa.Antineoplastic Agents, Alkylating: A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level.Stem Cell Transplantation: The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Translocation, Genetic: A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Combined Modality Therapy: The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.Recurrence: The return of a sign, symptom, or disease after a remission.Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.Chromosomes, Human, Pair 13: A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Hypergammaglobulinemia: An excess of GAMMA-GLOBULINS in the serum due to chronic infections or PARAPROTEINEMIAS.beta 2-Microglobulin: An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.Amyloidosis: A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Bone Marrow Examination: Removal of bone marrow and evaluation of its histologic picture.Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Receptors, Interleukin-6: Cell surface receptors that are specific for INTERLEUKIN-6. They are present on T-LYMPHOCYTES, mitogen-activated B-LYMPHOCYTES, and peripheral MONOCYTES. The receptors are heterodimers of the INTERLEUKIN-6 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR GP130.Chromosomes, Human, Pair 4: A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system.Receptor, Fibroblast Growth Factor, Type 3: A fibroblast growth factor receptor that regulates CHONDROCYTE growth and CELL DIFFERENTIATION. Mutations in the gene for fibroblast growth factor receptor 3 have been associated with ACHONDROPLASIA; THANATOPHORIC DYSPLASIA and NEOPLASTIC CELL TRANSFORMATION.In Situ Hybridization, Fluorescence: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.Immunoglobulin D: An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B LYMPHOCYTES.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Neoplasms, Plasma Cell: Neoplasms associated with a proliferation of a single clone of PLASMA CELLS and characterized by the secretion of PARAPROTEINS.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.Osteoclasts: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Immunoglobulins: Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.Hematopoietic Stem Cell Mobilization: The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.Peripheral Blood Stem Cell Transplantation: Transplantation of stem cells collected from the peripheral blood. It is a less invasive alternative to direct marrow harvesting of hematopoietic stem cells. Enrichment of stem cells in peripheral blood can be achieved by inducing mobilization of stem cells from the BONE MARROW.Transplantation Conditioning: Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Angiogenesis Inhibitors: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Immunoglobulin A: Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.Hematologic Neoplasms: Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic.Induction Chemotherapy: Initial drug treatment designed to bring about REMISSION INDUCTION. It is typically a short-term and high-dose drug treatment that is followed by CONSOLIDATION CHEMOTHERAPY and then MAINTENANCE CHEMOTHERAPY.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides.

Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. (1/5264)

Interleukin 6 (IL-6) is the major survival factor for myeloma tumor cells and induces signaling through the STAT proteins. We report that one STAT family member, Stat3, is constitutively activated in bone marrow mononuclear cells from patients with multiple myeloma and in the IL-6-dependent human myeloma cell line U266. Moreover, U266 cells are inherently resistant to Fas-mediated apoptosis and express high levels of the antiapoptotic protein Bcl-xL. Blocking IL-6 receptor signaling from Janus kinases to the Stat3 protein inhibits Bcl-xL expression and induces apoptosis, demonstrating that Stat3 signaling is essential for the survival of myeloma tumor cells. These findings provide evidence that constitutively activated Stat3 signaling contributes to the pathogenesis of multiple myeloma by preventing apoptosis.  (+info)

Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell. (2/5264)

Oncogenes are often dysregulated in B cell tumors as a result of a reciprocal translocation involving an immunoglobulin locus. The translocations are caused by errors in two developmentally regulated DNA recombination processes: V(D)J and IgH switch recombination. Both processes share the property of joining discontinuous sequences from one chromosome and releasing intervening sequences as circles that are lost from progeny cells. Here we show that these intervening sequences may instead insert in the genome and that during productive IgH mu-epsilon switch recombination in U266 myeloma tumor cells, a portion of the excised IgH switch intervening sequences containing the 3' alpha-1 enhancer has inserted on chromosome 11q13, resulting in overexpression of the adjacent cyclin D1 oncogene.  (+info)

Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma. (3/5264)

Immunohistochemical, cytochemical and ultrastructural data showing vivid angiogenesis and numerous mast cells (MCs) in the bone marrow of 24 patients with active multiple myeloma (MM) compared with 34 patients with non-active MM and 22 patients with monoclonal gammopathy of undetermined significance (MGUS) led us to hypothesize that angiogenesis parallels progression of MM, and that MCs participate in its induction via angiogenic factors in their secretory granules.  (+info)

Detection of Kaposi's sarcoma herpesvirus DNA sequences in multiple myeloma bone marrow stromal cells. (4/5264)

Whether Kaposi's sarcoma herpesvirus (KSHV) is associated with multiple myeloma (MM) remains controversial. We assayed for KSHV DNA sequences in long-term bone marrow stromal cells (BMSCs) from 26 patients with MM and 4 normal donors. Polymerase chain reaction (PCR) using primers which amplify a KSHV gene sequence to yield a 233-bp fragment (KS330233 within open reading frame 26) was negative in all cases. Aliquots of these PCR products were used as templates in subsequent nested PCR, with primers that amplify a 186-bp product internal to KS330233. BMSCs from 24 of 26 (92%) patients with MM and 1 of 4 normal donors were KSHV PCR+. DNA sequence analyses showed interpatient specific mutations (2 to 3 bp). Both Southern blot and sequence analyses confirmed the specificity of PCR results. The presence of the KSHV gene sequences was further confirmed by amplifying T 1.1 (open reading frame [ORF] K7) and viral cyclin D (ORF 72), two other domains within the KSHV genome. Immunohistochemical studies of KSHV PCR+ MM BMSCs demonstrate expression of dendritic cell (DC) lineage markers (CD68, CD83, and fascin). Serological studies for the presence of KSHV lytic or latent antibodies were performed using sera from 53 MM patients, 12 normal donors, and 5 human immunodeficiency virus (HIV)/KSHV+ patients. No lytic or latent antibodies were present in sera from either MM patients or normal donors. Taken together, these findings show that KSHV DNA sequences are detectable in BMSCs from the majority of MM patients, but that serologic responses to KSHV are not present. Ongoing studies are defining whether the lack of antibody response is caused by the absence of ongoing infection, the presence of a novel viral strain associated with MM, or underlying immunodeficiency in these patients.  (+info)

Bone marrow and peripheral blood dendritic cells from patients with multiple myeloma are phenotypically and functionally normal despite the detection of Kaposi's sarcoma herpesvirus gene sequences. (5/5264)

Multiple myeloma (MM) cells express idiotypic proteins and other tumor-associated antigens which make them ideal targets for novel immunotherapeutic approaches. However, recent reports show the presence of Kaposi's sarcoma herpesvirus (KSHV) gene sequences in bone marrow dendritic cells (BMDCs) in MM, raising concerns regarding their antigen-presenting cell (APC) function. In the present study, we sought to identify the ideal source of DCs from MM patients for use in vaccination approaches. We compared the relative frequency, phenotype, and function of BMDCs or peripheral blood dendritic cells (PBDCs) from MM patients versus normal donors. DCs were derived by culture of mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. The yield as well as the pattern and intensity of Ag (HLA-DR, CD40, CD54, CD80, and CD86) expression were equivalent on DCs from BM or PB of MM patients versus normal donors. Comparison of PBDCs versus BMDCs showed higher surface expression of HLA-DR (P =.01), CD86 (P =. 0003), and CD14 (P =.04) on PBDCs. APC function, assessed using an allogeneic mixed lymphocyte reaction (MLR), demonstrated equivalent T-cell proliferation triggered by MM versus normal DCs. Moreover, no differences in APC function were noted in BMDCs compared with PBDCs. Polymerase chain reaction (PCR) analysis of genomic DNA from both MM patient and normal donor DCs for the 233-bp KSHV gene sequence (KS330233) was negative, but nested PCR to yield a final product of 186 bp internal to KS330233 was positive in 16 of 18 (88.8%) MM BMDCs, 3 of 8 (37.5%) normal BMDCs, 1 of 5 (20%) MM PBDCs, and 2 of 6 (33.3%) normal donor PBDCs. Sequencing of 4 MM patient PCR products showed 96% to 98% homology to the published KSHV gene sequence, with patient specific mutations ruling out PCR artifacts or contamination. In addition, KHSV-specific viral cyclin D (open reading frame [ORF] 72) was amplified in 2 of 5 MM BMDCs, with sequencing of the ORF 72 amplicon revealing 91% and 92% homology to the KSHV viral cyclin D sequence. These sequences again demonstrated patient specific mutations, ruling out contamination. Therefore, our studies show that PB appears to be the preferred source of DCs for use in vaccination strategies due to the ready accessibility and phenotypic profile of PBDCs, as well as the comparable APC function and lower detection rate of KSHV gene sequences compared with BMDCs. Whether active KSHV infection is present and important in the pathophysiology of MM remains unclear; however, our study shows that MMDCs remain functional despite the detection of KSHV gene sequences.  (+info)

Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. (6/5264)

Integrin-mediated adhesion influences cell survival and may prevent programmed cell death. Little is known about how drug-sensitive tumor cell lines survive initial exposures to cytotoxic drugs and eventually select for drug-resistant populations. Factors that allow for cell survival following acute cytotoxic drug exposure may differ from drug resistance mechanisms selected for by chronic drug exposure. We show here that drug-sensitive 8226 human myeloma cells, demonstrated to express both VLA-4 (alpha4beta1) and VLA-5 (alpha5beta1) integrin fibronectin (FN) receptors, are relatively resistant to the apoptotic effects of doxorubicin and melphalan when pre-adhered to FN and compared with cells grown in suspension. This cell adhesion mediated drug resistance, or CAM-DR, was not due to reduced drug accumulation or upregulation of anti-apoptotic Bcl-2 family members. As determined by flow cytometry, myeloma cell lines selected for drug resistance, with either doxorubicin or melphalan, overexpress VLA-4. Functional assays revealed a significant increase in alpha4-mediated cell adhesion in both drug-resistant variants compared with the drug-sensitive parent line. When removed from selection pressure, drug-resistant cell lines reverted to a drug sensitive and alpha4-low phenotype. Whether VLA-4-mediated FN adhesion offers a survival advantage over VLA-5-mediated adhesion remains to be determined. In conclusion, we have demonstrated that FN-mediated adhesion confers a survival advantage for myeloma cells acutely exposed to cytotoxic drugs by inhibiting drug-induced apoptosis. This finding may explain how some cells survive initial drug exposure and eventually express classical mechanisms of drug resistance such as MDR1 overexpression.  (+info)

Overexpression of the receptor for hyaluronan-mediated motility (RHAMM) characterizes the malignant clone in multiple myeloma: identification of three distinct RHAMM variants. (7/5264)

The receptor for hyaluronan (HA)-mediated motility (RHAMM) controls motility by malignant cells in myeloma and is abnormally expressed on the surface of most malignant B and plasma cells in blood or bone marrow (BM) of patients with multiple myeloma (MM). RHAMM cDNA was cloned and sequenced from the malignant B and plasma cells comprising the myeloma B lineage hierarchy. Three distinct RHAMM gene products, RHAMMFL, RHAMM-48, and RHAMM-147, were cloned from MM B and plasma cells. RHAMMFL was 99% homologous to the published sequence of RHAMM. RHAMM-48 and RHAMM-147 variants align with RHAMMFL, but are characterized by sequence deletions of 48 bp (16 amino acids [aa]) and 147 bp (49 aa), respectively. The relative frequency of these RHAMM transcripts in MM plasma cells was determined by cloning of reverse-transcriptase polymerase chain reaction (RT-PCR) products amplified from MM plasma cells. Of 115 randomly picked clones, 49% were RHAMMFL, 47% were RHAMM-48, and 4% were RHAMM-147. All of the detected RHAMM variants contain exon 4, which is alternatively spliced in murine RHAMM, and had only a single copy of the exon 8 repeat sequence detected in murine RHAMM. RT-PCR analysis of sorted blood or BM cells from 22 MM patients showed that overexpression of RHAMM variants is characteristic of MM B cells and BM plasma cells in all patients tested. RHAMM also appeared to be overexpressed in B lymphoma and B-chronic lymphocytic leukemia (CLL) cells. In B cells from normal donors, RHAMMFL was only weakly detectable in resting B cells from five of eight normal donors or in chronically activated B cells from three patients with Crohn's disease. RHAMM-48 was detectable in B cells from one of eight normal donors, but was undetectable in B cells of three donors with Crohn's disease. RHAMM-147 was undetectable in normal and Crohn's disease B cells. In situ RT-PCR was used to determine the number of individual cells with aggregate RHAMM transcripts. For six patients, 29% of BM plasma cells and 12% of MM B cells had detectable RHAMM transcripts, while for five normal donors, only 1. 2% of B cells expressed RHAMM transcripts. This work suggests that RHAMMFL, RHAMM-48, and RHAMM-147 splice variants are overexpressed in MM and other B lymphocyte malignancies relative to resting or in vivo-activated B cells, raising the possibility that RHAMM and its variants may contribute to the malignant process in B-cell malignancies such as lymphoma, CLL, and MM.  (+info)

Ibandronate reduces osteolytic lesions but not tumor burden in a murine model of myeloma bone disease. (8/5264)

We determined the effects of the potent bisphosphonate ibandronate in a murine model of human myeloma bone disease. In this model, bone lesions typical of the human disease develop in mice following inoculation of myeloma cells via the tail vein. Treatment with ibandronate (4 micrograms per mouse per day) significantly reduced the occurrence of osteolytic bone lesions in myeloma-bearing mice. However, ibandronate did not prevent the mice from developing hindlimb paralysis and did not produce a detectable effect on survival. There was no significant effect of ibandronate on total myeloma cell burden, as assessed by morphometric measurements of myeloma cells in the bone marrow, liver, and spleen, or by measurement of serum IgG2b levels. These results support clinical findings that bisphosphonates may be useful for the treatment of myeloma-associated bone destruction, but suggest that other therapies are also required to reduce tumor growth.  (+info)

  • According to the American Cancer Society, there are three stages of multiple myeloma. (reference.com)
  • Because plasma cells are part of the immune system and produce antibodies (disease-fighting proteins), the development of myeloma results in an impaired immune system with problems associated with an unbalanced antibody response, as well as other problems as associated with other types of cancer , including pain and weakness. (emedicinehealth.com)
  • Multiple myeloma is a cancer of the plasma cells. (mayo.edu)
  • The American Cancer Society estimates 20,000 people are diagnosed with multiple myeloma in the U.S. each year. (mayo.edu)
  • Stage II or III multiple myeloma is characterized by an intermediate or high amount of cancer in the body. (lacancernetwork.com)
  • A team of Mayo Clinic Cancer Center scientists has been awarded a Specialized Program of Research Excellence (SPORE) grant in multiple myeloma from the National Cancer Institute . (mayocliniclabs.com)
  • The Mayo Clinic Cancer Center is one of only three cancer centers to receive a SPORE grant for multiple myeloma cancer research. (mayocliniclabs.com)
  • 2017. "Whole-body MRI, Dynamic Contrast-enhanced MRI, and Diffusion-weighted Imaging for the Staging of Multiple Myeloma. (ugent.be)
  • Therefore, new strategies especially for relapsed and refractory and high-risk multiple myeloma (RRMM, HRMM) patients, who have poor response to current therapies, are required. (utupub.fi)
  • During the early stages of multiple myeloma, no symptoms may be apparent. (reference.com)
  • What are the stages of multiple myeloma? (reference.com)
  • It reviews the diagnostic performance, prognostic value, and role in therapy assessment in multiple myeloma and its precursor stages. (ugent.be)
  • People with MGUS do not have symptoms associated with multiple myeloma. (mayo.edu)
  • J. Abdi, J. Garssen and F. Redegeld, "Toll-Like Receptors in Human Multiple Myeloma: New Insight into Inflammation-Related Pathogenesis", Current Molecular Medicine (2014) 14: 423. (eurekaselect.com)
  • To investigate the patterns of genetic lesions in a panel of 23 human multiple myeloma cell lines (HMCLs), we made a genomic integrative analysis involving FISH, and both gene expression and genome-wide profiling approaches. (unimi.it)
  • In 2016, Myeloma Canada produced two patient submissions to pCODR for daratumumab, in combination with dexamethasone, and one for ixazomib plus lenalidomide (Revlimid®) and dexamethasone. (newswire.ca)
  • In 2016, the American Cancer Society estimates that 30,330 new multiple myeloma cases will be diagnosed and 12,650 cancer deaths due to multiple myeloma would occur. (cancerquest.org)
  • About 70% of individuals with multiple myeloma have soft spots or lesions in their bones. (encyclopedia.com)
  • Multiple myeloma (MM) is a malignancy of plasma cells characterized by growth in the bone marrow (BM) environment and the development of lytic lesions in the skeleton. (springer.com)
  • Multiple myeloma can cause soft spots in the bone called osteolytic lesions, which appear as holes on an X-ray . (healthline.com)
  • Radiologically, multiple destructive lytic lesions of the skeleton, as well as severe demineralization, characterize multiple myeloma. (medscape.com)
  • Although the osseous structures may appear radiographically normal or simply osteopenic, the classic appearance is of multiple, discrete, small, lytic lesions. (medscape.com)
  • A bone scan may show which bones are involved with multiple myeloma, but often the lesions cannot be seen. (aaos.org)
  • These x-rays show typical lesions caused by multiple myeloma. (aaos.org)
  • A mnemonic sometimes used to remember some of the common symptoms of multiple myeloma is CRAB: C = calcium (elevated), R = renal failure, A = anemia, B = bone lesions. (wikipedia.org)
  • On admission, initial NECT of the abdomen and pelvis demonstrated multiple osteolytic lesions in the pelvis, right femur, and lumbar spine with associated soft-tissue component and mass effect compromising the spinal canal at L1 (Figure 1). (appliedradiology.com)
  • MRI of the lumbar spine demonstrated multiple, multilevel T1 and T2 hypointense lesions and pathologic compression fracture with posterior expansile mass at L1 causing severe spinal and neural foraminal stenosis (Figure 2). (appliedradiology.com)
  • Subsequent myeloma work-up with a radiographic bone survey redemonstrated multiple osteolytic lesions throughout the lumbar spine, pelvis, and bilateral proximal femurs (Figure 4). (appliedradiology.com)
  • On imaging, multiple myeloma is hallmarked by focal or diffuse marrow infiltration and well-circumscribed osteolytic lesions. (appliedradiology.com)
  • Skeletal radiographs are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis. (aafp.org)
  • The International Myeloma Working Group (IMWG) was formed by the IMF to encourage dialog and collaboration among the world's leading myeloma experts. (myeloma.org)
  • A focal lytic lesion must be 5 mm or greater in size to be considered a true abnormality by the latest International Myeloma Working Group (IMWG) criteria. (medscape.com)
  • Dimopoulos et al (writing for the International Myeloma Working Group) reviewed the literature of all imaging modalities used in multiple myeloma and provided recommendations for each modality. (medscape.com)
  • Multiple myeloma is the second most common (10-15% of all) haematological cancer. (bmj.com)
  • Although myeloma remains an incurable cancer, survival is improving, and newly diagnosed patients are now projected to live for around five years. (bmj.com)
  • Multiple myeloma is a cancer in which antibody-producing plasma cells grow in an uncontrolled and invasive (malignant) manner. (encyclopedia.com)
  • Multiple myeloma , also known as plasma cell myeloma, is the second-most common cancer of the blood. (encyclopedia.com)
  • Multiple myeloma accounts for approximately 1% of all cancers and 2% of all deaths from cancer. (encyclopedia.com)
  • Multiple myeloma is one of the leading causes of cancer deaths among African Americans . (encyclopedia.com)
  • 3 After initial therapy, it is common for individuals with multiple myeloma to become less responsive to therapy or eventually experience a relapse, when the cancer returns. (novartis.com)
  • Multiple myeloma is a cancer that forms in a type of white blood cell called a plasma cell. (mayoclinic.org)
  • Multiple myeloma causes cancer cells to accumulate in the bone marrow, where they crowd out healthy blood cells. (mayoclinic.org)
  • Multiple myeloma is a cancer of certain cells of the bone marrow called plasma cells. (medicinenet.com)
  • Multiple myeloma is a form of bone marrow cancer . (medicinenet.com)
  • The American Cancer Society (ACS) estimates the risk of developing multiple myeloma over a lifetime as 1 in 143 or 0.7 percent . (medicalnewstoday.com)
  • Multiple myeloma is a type of cancer. (medicalnewstoday.com)
  • The signs and symptoms of multiple myeloma depend on the stage of the cancer and the general health of the patient. (medicalnewstoday.com)
  • Multiple myeloma is not usually curable and treatment is therefore aimed at delaying the progression of the cancer for as long as possible. (news-medical.net)
  • Cancer Care provides free, professional support services for people affected by multiple myeloma, as well as multiple myeloma treatment information and additional resources. (cancercare.org)
  • Savage D, Garrett TJ (1986) Multiple myeloma masquerading as metastatic breast cancer. (springer.com)
  • Multiple myeloma is a cancer of the blood (hematologic cancer) in which one population of clonal (identical) plasma cells starts to reproduce uncontrollably. (oncolink.org)
  • Scientists from The Institute of Cancer Research in the UK found a genetic variant called TERC among four new variants that they linked to multiple myeloma - a form of cancer that affects immune cells produced in the bone marrow for circulation in the blood. (medicalnewstoday.com)
  • Myeloma is a relatively uncommon cancer according to the American Cancer Society statistics, with a 1 in 149 risk of developing the disease in the US. (medicalnewstoday.com)
  • For the study, the research team analyzed the genetic make-up of 4,692 patients who had myeloma, and compared this with DNA of 10,990 people who did not have the blood cancer. (medicalnewstoday.com)
  • Richard Houlston, professor of molecular and population genetics at The Institute of Cancer Research ( ICR ), explains: "Our study has taken an important step forward in understanding the genetics of myeloma, and suggested an intriguing potential link with a gene that acts as a cell's internal timer. (medicalnewstoday.com)
  • If the cancer has spread, see Guide 1 on page 16 for recommended testing to assess the severity of multiple myeloma and its symptoms. (nccn.org)
  • Next steps  If tests show the cancer has spread, the next treatment options depend on the severity of myeloma and its symptoms. (nccn.org)
  • According to Stanford University, multiple myeloma is rare, accounting for only 1 percent of all cancer cases in the United States. (healthline.com)
  • Among the many frustrating things about the blood cancer known as multiple myeloma is the fact that it's hard to predict who will get it. (healthcentral.com)
  • But multiple myeloma cancer cells are often found to have an extra chromosome or may be missing a part of one chromosome. (healthcentral.com)
  • Reuters) - Amgen Inc's Kyprolis drug failed to extend survival compared to standard care in a trial involving patients with advanced multiple myeloma, a type of blood cancer that develops in the bone marrow. (yahoo.com)
  • The physicians and researchers in the Malignant Hematology Program at Moffitt Cancer Center are working to develop new and better multiple myeloma screening techniques in order to detect and address the condition as early as possible. (moffitt.org)
  • According to the American Cancer Society, in 2015 about 26,850 people will be diagnosed with multiple myeloma (14,090 men and 12,760 women). (nurse.com)
  • Multiple myeloma is a cancer that starts in plasma cells. (cancer.ca)
  • Multiple myeloma is a serious condition on its own, but both the cancer and the resulting bone damage can lead to several serious long-term effects. (healthline.com)
  • The Malignant Hematology Program at Moffitt Cancer Center is dedicated to the research and treatment of all forms of hematologic cancer, including multiple myeloma. (moffitt.org)
  • Each year, more than 25,000 Americans are diagnosed with multiple myeloma, a form of blood cancer that often develops resistance to therapies. (eurekalert.org)
  • Not only was the combination therapy effective against multiple myeloma cells, it notably did not harm normal bone marrow cells, raising the possibility of therapeutic selectivity," says Grant, the study's lead investigator and Shirley Carter Olsson and Sture Gordon Olsson Chair in Cancer Research, associate director for translational research and program co-leader of Developmental Therapeutics at VCU Massey Cancer Center. (eurekalert.org)
  • Researchers have discovered why multiple myeloma, a difficult to cure cancer of the bone marrow, frequently recurs after an initially effective treatment that can keep the disease at bay for up to several years. (redorbit.com)
  • The research team initially analyzed 7,500 genes in multiple myeloma cells to identify genes which when suppressed made cancer cells resistant to a common class of drugs called proteasome inhibitors such as bortezomib or carfilzomib. (redorbit.com)
  • According to the American Cancer Society, there are three stages of multiple myeloma. (reference.com)
  • The survival rates for multiple myeloma are 62, 44 and 29 months for stages one, two and three, respectively, according to Cancer.org. (reference.com)
  • Multiple myeloma is a form of cancer that is caused by the malignant and abnormal growth of plasma cells. (thirdage.com)
  • The most comprehensive genetic study to date of the blood cancer multiple myeloma has revealed that the genetic landscape of the disease may be more complicated than previously thought. (eurekalert.org)
  • What this new work shows us is that when we treat an individual patient with multiple myeloma, it's possible that we're not just looking at one disease, but at many - in the same person, there could be cancer cells with different genetic make-ups," said co-senior author Todd Golub, the Broad Institute's Chief Scientific Officer and Charles A. Dana Investigator in Human Cancer Genetics at the Dana-Farber Cancer Institute. (eurekalert.org)
  • In a detailed study of samples from more than 200 multiple myeloma patients, Golub and colleagues identified frequent mutations in several key genes known to play an important role in cancer including KRAS, NRAS, and BRAF. (eurekalert.org)
  • In laboratory experiments, multiple myeloma patients had increased levels of sclerostin, which correlated with tumor burden, Homare Eda, MD, PhD, research fellow in cancer at Harvard Medical School in Boston, told MedPage Today . (medpagetoday.com)
  • David Vesole, MD, PhD, co-chief of the myeloma division at John Theurer Cancer Center at Hackensack University Hospital, New Jersey, noted that scientists have been looking for various targets in multiple myeloma and have had success in finding substances in the laboratory that seem like promising targets. (medpagetoday.com)
  • They determined that blood plasma sclerostin levels were higher in the multiple myeloma patients when compared to three leukemia patients, 40 gastric cancer patients, and four healthy volunteers. (medpagetoday.com)
  • Multiple myeloma is a type of cancer that forms in plasma cells (also called mature B-lymphocytes), which are a type of white blood cell that is made in the bone marrow. (drugs.com)
  • If there's one disease that most shows the effects of recent improvements in cancer treatment, it's multiple myeloma. (harvard.edu)
  • The reason, explains research published online today in Cancer Cell , is intrinsic resistance found in immature progenitor cells that are the root cause of the disease - and relapse - says principal investigator Dr. Rodger Tiedemann, a hematologist specializing in multiple myeloma and lymphoma at the Princess Margaret, University Health Network (UHN). (medindia.net)
  • Over time, myeloma recurs and arises because small areas of this cancer may remain undetected and resistant to treatment in the body. (cancer.net)
  • Multiple myeloma is an uncommon cancer. (cancervic.org.au)
  • Multiple myeloma (also known as "myeloma") is the most common primary bone cancer. (aaos.org)
  • Multiple myeloma is named for the "clock face" appearance of the cancer cells when seen under a microscope. (aaos.org)
  • Aflibercept may be able to carry cancer-killing substances directly to multiple myeloma cells. (clinicaltrials.gov)
  • It may also stop the growth of multiple myeloma by blocking blood flow to the cancer. (clinicaltrials.gov)
  • MONTREAL , July 4, 2017 /CNW/ - Multiple myeloma, commonly referred to as myeloma, is an incurable cancer of the plasma cells found in the bone marrow. (newswire.ca)
  • Myeloma Canada is a non-profit, charitable organization created by, and for people living with multiple myeloma, a relatively unknown cancer of the plasma cells. (newswire.ca)
  • Learn more about multiple myeloma or make an appointment at the Winship Cancer Institute of Emory University . (cancerquest.org)
  • The study, a collaborative effort among researchers from Moffitt, Dana-Farber Cancer Institute, Hackensack University Medical Center, Multiple Myeloma Research Consortium, and Celgene Corporation, appeared in the Dec. 14 issue of Blood, the journal of the American Society of Hematology. (innovations-report.com)
  • The novel platform, created by Mount Sinai cancer, genomics, and precision health researchers, expands on traditional DNA-based approaches by using RNA sequencing to find targets for a broad swath of FDA-approved cancer drugs beyond those approved specifically for multiple myeloma. (nursingcenter.com)
  • This approach was tested in a pilot precision medicine clinical trial with 64 patients with late-stage and drug resistant multiple myeloma, the second most common blood cancer. (nursingcenter.com)
  • Our study shows how a precision medicine approach incorporating RNA sequencing may identify viable and effective therapeutic options beyond the current FDA-approved armamentarium for multiple myeloma patients," said researcher Samir Parekh, MD, Associate Professor of Medicine (Hematology and Medical Oncology) and Oncological Sciences and Director of Translational Research in Myeloma at The Tisch Cancer Institute in the Icahn School of Medicine at Mount Sinai. (nursingcenter.com)
  • Research investigators have identified molecular changes in multiple myeloma cells that activate an important biological pathway associated with cell growth and survival, thereby revealing potential new targets for drugs to treat this cancer. (emaxhealth.com)
  • The researchers, led by a team from the National Cancer Institute (NCI), part of the National Institutes of Health, have shown that malignant cells in multiple myeloma frequently harbor mutations that activate what is called the NF-kappaB signaling pathway, which plays a key role in promoting cell growth and preventing programmed cell death. (emaxhealth.com)
  • This is one of the largest collaborative translational cancer research efforts of its kind," said John Shaughnessy, Jr., Ph.D., director of the Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics and chief of Basic Sciences at the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences, Little Rock, Ark. (emaxhealth.com)
  • Multiple myeloma, a cancer of plasma cells inside the bone marrow, is relatively uncommon but often fatal: About 24,000 people are diagnosed with multiple myeloma in the United States each year. (lifescript.com)
  • As explained in the Introduction , a person with a small amount of M protein in his or her blood has a 1% to 2% chance of developing myeloma, lymphoma , or another blood-related cancer called Waldenstrom's macroglobulinemia per year (see the Stages section for more information). (cancer.net)
  • A clinician who specializes in diseases of the blood, Chapman sees many patients with multiple myeloma - an incurable blood cancer that springs from plasma cells (a type of white blood cell) that have gone awry. (broadinstitute.org)
  • Multiple myeloma is the second most common blood cancer in the United States and causes about 20,000 new cases in this country every year. (broadinstitute.org)
  • These genes, which are frequently mutated, were not on anyone's radar before when thinking about multiple myeloma specifically or cancer in general," said Golub, who is also an investigator at Howard Hughes Medical Institute, and professor of pediatrics at Harvard Medical School. (broadinstitute.org)
  • Professor Chris Bunce, research director at Leukemia & Lymphoma Research , says this research offers more evidence that the risk of myeloma can be inherited. (medicalnewstoday.com)
  • The LLS mission: Cure leukemia, lymphoma, Hodgkin's disease and myeloma, and improve the quality of life of patients and their families. (lls.org)
  • Multiple myeloma often times originates in the bone marrow and is similar to diseases such as leukemia and lymphoma. (reference.com)
  • a U.S. specialty pharmaceutical company and Clinigen Group plc (AIM: CLIN, 'Clinigen') , the global pharmaceutical and services company, announce a new publication in Leukemia & Lymphoma , with study results showing that amifostine decreases gastro-intestinal (GI) toxicity in patients who receive treatment for their multiple myeloma. (prnewswire.com)
  • Beyond a broad spectrum of related plasma cell disorders that are differentiated based on laboratory and clinical findings, the primary differential considerations for multiple myeloma are metastases and lymphoma/leukemia. (appliedradiology.com)
  • In an interview, Congress Chair Morton Coleman, MD, Director of the Center for Lymphoma and Myeloma at New York-Presbyterian Hospital/Weill Cornell Medical College, agreed: "We are looking for an R-CHOP-like therapy in myeloma. (lww.com)
  • Sequencing multiple tumor genomes] enabled us to pick out which genes are significantly, recurrently mutated in ways that we couldn't have with a single genome," said Chapman, who is supported by a Clinician Scientist Fellowship from Leukaemia and Lymphoma Research. (broadinstitute.org)
  • The cause of multiple myeloma is unclear. (medlineplus.gov)
  • The exact cause of multiple myeloma is not known as of 2015, states Mayo Clinic. (reference.com)
  • The incidence of multiple myeloma has been steadily increasing each year. (nurse.com)
  • Occupational exposure - The incidence of multiple myeloma tends to be higher than average among people in certain occupations, including agricultural and farm workers, cosmetologists, petroleum workers and employees in the leather industry. (moffitt.org)
  • There is an increased incidence of multiple myeloma in persons with rheumatoid arthritis or obesity (body mass index of more than 30 kg per m 2 ). (aafp.org)
  • These chromosome abnormalities may be an explanation for the wide variation in response to treatment among individuals with multiple myeloma. (healthcentral.com)
  • In Western industrialized countries, approximately four people in 100,000 develop multiple myeloma. (encyclopedia.com)
  • Black people are about twice as likely to develop multiple myeloma as are white people. (mayoclinic.org)
  • African Americans are more than twice as likely to develop multiple myeloma than white Americans. (thirdage.com)
  • Only 20% of people with myeloma have this kind. (webmd.com)
  • This rare type affects only 1% to 2% of all people with myeloma. (webmd.com)
  • Age is a risk factor for myeloma, with 96 percent of people with myeloma aged over 45 years. (medicalnewstoday.com)
  • Our specialists monitor people with myeloma who are being cared for at home in collaboration with local infusion companies, visiting nurses, and hospice workers. (mskcc.org)
  • They are often prescribed to control pain in people with myeloma. (mskcc.org)
  • These data demonstrate that increased sclerostin levels in multiple myeloma patients inhibit osteoblastogenesis and stimulate osteoclastogenesis," he suggested. (medpagetoday.com)
  • NEW YORK (GenomeWeb) - Researchers from Erasmus MC University Medical Center and Radboud University Medical Center in The Netherlands have developed a mass spec-based test for measuring M protein levels in multiple myeloma patients. (genomeweb.com)
  • Anti-nausea drug thalidomide when combined with turmeric can effectively kill multiple myeloma cells, say researchers. (medindia.net)
  • Here we review the current understanding of myeloma pathogenesis and insight into new therapeutic strategies provided by animal models and genetic screens. (jci.org)
  • 1,2 The exact pathogenesis of multiple myeloma is unknown, but there is increased incidence in males and African Americans as well as with exposure to various environmental factors. (appliedradiology.com)
  • The aberrant role of miRNAs has been reported in a number of hematopoietic malignancies including multiple myeloma (MM). In this review we summarize the current knowledge on roles of miRNAs in the pathogenesis of MM. (frontiersin.org)
  • The study concluded that amifostine therapy decreased GI toxicity without any significant adverse effects while preserving the anti-myeloma efficacy of high-dose melphalan and auto-HTC. (prnewswire.com)
  • Noopur Raje, MD, assistant professor of medicine and director of the Center for Multiple Myeloma at Massachusetts General Hospital/Harvard Medical School said, however, that cost was often not a major factor in selection of treatment regimens for multiple myeloma. (medpagetoday.com)
  • Kyprolis, acquired by Amgen in its $10 billion takeover of Onyx Pharmaceuticals, was approved in the United States for treating advanced multiple myeloma based on data showing that patients responded to the drug. (yahoo.com)
  • The Total Therapy treatment regimens developed at the Myeloma Institute have demonstrated great improvement in treatment outcomes for multiple myeloma patients. (clinicaltrials.gov)
  • Nongenetic factors that increase the risk of developing multiple myeloma include previous radiation therapy or other radiation exposure. (medlineplus.gov)
  • Today we approved a treatment under our accelerated approval program that provides a treatment option for patients with multiple myeloma with no available therapy. (fda.gov)
  • On the basis of these results, the company has submitted an approval application to the US Food and Drug Administration for use of belantamab mafodotin in the treatment of patients with relapsed or refractory multiple myeloma whose prior therapy includes an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. (medscape.com)
  • [ 9 ] MRI is the gold-standard imaging modality for detection of bone marrow involvement and the preferred imaging technique to rule out spinal cord compression in patients with multiple myeloma, whereas PET/CT provides valuable prognostic data and aids in assessment of response to therapy. (medscape.com)
  • The new findings will not immediately change the treatment options for Chapman's patients - although there is a glimmer of promise for some that could result in a new, more effective therapy - but the results are already impacting the future of multiple myeloma research. (broadinstitute.org)