Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the last decade, the availability of large numbers of cytokines and growth factors has greatly favoured the use of biotherapies in several haematological disease. For MM, the majority of clinical studies have dealt with the use of IFN-alpha. From these studies it appears that IFN-alpha has a definite role in the treatment of MM especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies or HDC followed by BMT procedures or PBSCI. Data on the use of EPO have consistently demonstrated the role of this growth factor in ameliorating the grade of anaemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Despite the large amount of experimental data indicating a role for IL-2 and IL-6 in controlling tumour growth, there are only a few clinical studies dealing with their use in MM. From these, it appears that IL-2 and anti-IL-6 antibodies should be further investigated as therapeutic tools useful in maintaining responses, because results show that they arrest tumour progression rather than aid, tumour regression. Finally, in the next years, there will be a wider diffusion of biotherapies in MM that should take into account the roles that IL-1 beta and TNF alpha play in myeloma cell proliferation and bone destruction and the finding that retinoic acid is capable of inhibiting the growth of human myeloma cells in vitro through modulation of IL-6 and its receptor.
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PMID:The role of biotherapies (interleukins, interferons and erythropoietin) in multiple myeloma. 884 74

The Polyneuropathy, Organomegaly, Endocrinopathy, M protein, Skin changes (POMEMS) syndrome is a rare multisystem disorder of obscure pathogenesis, associated with osteosclerotic myeloma. Unlike multiple myeloma without neuropathy, circulating levels of proinflammatory cytokines (IL-1 beta, TNF-alpha IL-6) are increased in patients with POEMS syndrome. Sites of IL-1 beta production include lymph node and bone marrow tissues. These data support the view that pleiotropic effects of proinflammatory cytokines released secondary to a strong activation of the monocyte/macrophage system, take part in the multisystemic expression of the disease.
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PMID:[Pro-inflammatory cytokines: a pathogenic key of POEMS syndrome]. 888 41

Cytokine messenger RNA expression was studied using the reverse transcription/polymerase chain reaction in 23 patients with multiple myeloma (MM), 16 with monoclonal gammopathy of undetermined significance (MGUS), 12 with post menopausal osteoporosis, (OP) and 12 normal controls. Messenger RNAs for IL-1 alpha, IL-1 beta, TNF-alpha, TNF-beta, IL-6 and M-CSF were sought in view of their reported pathogenic role in myeloma. Transcripts for IL-1 beta, TNF-alpha, TNF-beta and M-CSF were found frequently in all four groups of patients. The only significant difference in cytokine expression between the groups was for IL-6 which was expressed in 17% of controls compared with 87% of patients with MM (p < 0.001), 62% of patients with MGUS (p < 0.02) and 67% of patients with osteoporosis (p < 0.02). Further analysis of IL-6 expression by quantitative PCR showed significantly higher IL-6 mRNA levels in MM compared with MGUS (p < 0.006). There was no correlation however between expression of individual cytokines and clinical features of myeloma such as osteolytic bone disease or hypercalcaemia. We conclude that expression of IL-6 mRNA is significantly enhanced in multiple myeloma when compared with MGUS. However, since MGUS and osteoporosis were also associated with a high prevalence of IL-6 expression when compared with controls it is probable that factors other than IL-6 are responsible for the local osteolytic lesions which characterise MM, but which are not seen in MGUS or osteoporosis.
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PMID:Cytokine expression in multiple myeloma and monoclonal gammopathy: analysis by reverse transcription/polymerase chain reaction and quantitative PCR. 904 67

The ST2 gene, which is specifically induced by growth stimulation, encodes interleukin-1 receptor-related proteins. Using the RT-PCR method, we found that the ST2 gene was broadly expressed in hematopoietic cell lines. It was also expressed specifically in helper T cell lines among lymphocytic cell lines. We analyzed the expression of ST2 in mouse helper T cell subsets with Northern blotting analysis. Mouse Th1 cell lines so far studied did not express ST2 mRNAs. On the other hand, one of the Th2 cell lines, D10, expressed ST2L (transmembrane form) without stimulation, while co-stimulation by PMA and A23187 induced ST2 (soluble form) mRNA. These results suggest that the ST2 gene is involved in the regulation of the immune system. IL-1 alpha, IL-1 beta, and receptor antagonist did not bind to ST2L protein, which prompted us to search for the specific ligand of ST2. The recombinant human ST2 protein was purified and labeled with FITC. The labeled human ST2 protein bound with myeloma-derived RPMI8226 cells among the various B-cell lines, indicating possible involvement of ST2 in T-cell/B-cell interaction.
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PMID:The expression of ST2 gene in helper T cells and the binding of ST2 protein to myeloma-derived RPMI8226 cells. 905 98

Gaucher's disease is characterized by hepatosplenomegaly, bone-marrow infiltration, osteonecrosis and bone thinning, associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. To investigate the possible role of cytokines in the systemic and local manifestations of established Gaucher's disease, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10) were measured in freshly-separated serum. Samples from eight male and 14 female patients with type 1 Gaucher's disease were compared with sera from 22 healthy age- and sex-matched controls. Concentrations of IL-6 and IL-10 were significantly elevated in sera from patients with Gaucher's disease (11.9 +/- 1.8 (SEM) pg/ml and 5.4 +/- 0.5 (SEM) pg/ml, respectively) compared with those of controls (4.1 +/- 0.9 (SEM) and 0.8 +/- 0.3 (SEM) pg/ml, p < 0.0001). No significant differences in concentrations of TNF alpha or IL-1 beta were identified. IL-6 has been implicated in the development of localized osteolysis in multiple myeloma and in the development of post-menopausal osteoporosis. High concentrations of IL-6 in the serum of patients with Gaucher's disease may thus reflect the development of the bone lesions commonly associated with this disorder. Since IL-6 and IL-10 are important regulators of lymphocyte growth and differentiation, and IL-6 concentrations were significantly raised in patients with oligo- or polyclonal increases in serum immunoglobulins, enhanced release of these cytokines from pathological macrophages provides a pathological link between Gaucher's disease and associated lympho-proliferative disorders.
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PMID:Pro-inflammatory cytokines and the pathogenesis of Gaucher's disease: increased release of interleukin-6 and interleukin-10. 909 85

POEMS syndrome is an acronym defined by Bardwick (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal component and Skin changes). Other various clinical and biological features are reported: edema, cachexia, microangiopathic glomerulopathy, most rarely pulmonary hypertension, cutaneous necrosis. Thrombocytosis or polycythemia may be a prominent feature. POEMS syndrome is sometimes associated with lymphoproliferative disorder. Castelman-like disease is frequently observed as pathologic findings on lymph nodes. Distinction between POEMS syndrome and osteosclerotic myeloma is delicate. The rate of the monoclonal protein is modest-always less than 30 g/L-and is almost of the lambda light chain class. In contrast to multiple myeloma this syndrome is rarely associated with hypercalcemia, skeletal fracture, renal involvement and increasing of M component during evolution. Bone marrow plasmocytosis is usually less than 15% and the kinetic phenotype and genetic characteristics of the plasma cell remain those found in monoclonal gammopathy of undetermined significance. The pathophysiology of this syndrome remains largely unknown but overproduction of pro-inflammatory cytokines are reported, especially TNF alpha, IL-6 and IL-1 beta. Some clinical manifestations seem to be cytokine related. Polyneuropathy and cachexia are the main cause of death. A part corticosteroid and cure of solitary bone lesion, treatment is disappointing and survival is 60% at five years.
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PMID:[POEMS syndrome]. 925 73

Interleukin-1 beta has potent OAF activity, can increase the expression of adhesion molecules, and can induce paracrine IL-6 production (see Fig. 1). These biologic effects of IL-1 beta closely parallel several of the clinical features of human myeloma, such as osteolytic bone lesions, homing of myeloma cells to the bone marrow, and IL-6-induced cell growth. The increased production of adhesion molecules could explain why myeloma cells are found predominantly in the bone marrow. These fixed monoclonal plasma cells could subsequently stimulate osteoclasts through the production of IL-1 beta and paracrine generation of IL-6, resulting in osteolytic disease. Also, IL-6 produced by either a paracrine or autocrine mechanism can support the growth of the myeloma cells that may be manifested clinically by an elevated labeling index. In the future, continued follow-up of IL-1 beta-positive and IL-1 beta-negative MGUS patients should determine whether aberrant expression of IL-1 beta by monoclonal plasma cells is a critical genetic event in the progression of MGUS to myeloma. Because MGUS is relatively common in the general population and myeloma is incurable in almost all cases, identification of MGUS patients who are likely to progress to active myeloma will be important in the development of new therapeutic strategies. For example, an effective chemopreventive agent that prevents or delays the transition from MGUS to myeloma could have a major effect on the treatment of patients with monoclonal gammopathies.
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PMID:The role of interleukin-1 beta in the pathogenesis of multiple myeloma. 1062 39

Poems syndrome is a rare multisystemic disorder. It manifestations are Polyneuropathy, Organomegaly, Endocrinopathy, and/or Edema, Monoclonal protein and changes in the Skin. (P.O.E.M.S.) Though some bibliography make no difference with osteoesclerotic myeloma it is considered a real syndrome. The polyneuropathy is customarily severe. Although high levels of immunoglobulins has been found in the poems, it has not been isolated a specific antibody that explain the polyneuropathy even though it is strongly suspected. The organomegaly, endocrinopathy, changes in the skin and other systems and involved organs could be in relationship to products secreted by plasmatic cells. We review the physiopathology and bibliography of the Poems, especially its neurological expression its nosologic location different from osteosclerotic myeloma and a possible relationship to the Herpes Virus 8. It was crossed in Medline the terms P.O.E.M.S. and syndrome and were obtained 271 abstracts that were all examined and finally selected the bibliography considerate meaningful for the objectives. It is presented briefly a case. P.O.E.M.S. is a syndrome that is associated to multiple plasma cell dyscracia, included the osteoesclerotic myeloma. Prognosis and the treatment vary with the underlying disease. As physiopathology of this syndrome is insinuated the action of the interleukins 1-beta (IL-1 beta) and 6 (IL-6), the vascular growth endothelial factor (VGEF), the tumoral necrosis factor alpha (TNF-alpha) and antibodies anti-nerve. The P.O.E.M.S. is a syndrome with own identity. The Herpes Virus 8 may plays a key rol to uncover the Poems physiopathology.
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PMID:[POEMS syndrome]. 1088 13

This study was designed to determine if macrophage inhibitory protein-1 alpha (MIP-1 alpha), a recently described osteoclast (OCL) stimulatory factor,(1) was present in marrow from patients with multiple myeloma (MM) and possibly involved in the bone destructive process. MIP-1 alpha, but not interleukin-1 beta (IL-1 beta), tumor necrosis factor-beta (TNF-beta), or interleukin-6 (IL-6), messenger RNA was elevated in freshly isolated bone marrow from 3 of 4 patients with MM compared to normal controls. Furthermore, enzyme-linked immunosorbent assays of freshly isolated bone marrow plasma detected increased concentrations of hMIP-1 alpha (range, 75-7784 pg/mL) in 8 of 13 patients (62%) with active myeloma, in 3 of 18 patients (17%) with stable myeloma (range, 75-190.3), as well as in conditioned media from 4 of 5 lymphoblastoid cell lines (LCLs) derived from patients with MM. Mildly elevated levels of MIP-1 alpha were detected in 3 of 14 patients (21%) with other hematologic diagnoses (range, 80.2-118.3, median value of 96 pg/mL) but not in normal controls (0 of 7). MIP-1 alpha was not detected in the peripheral blood of any patients with MM. In addition, recombinant hMIP-1 alpha induced OCL formation in human bone marrow cultures. Importantly, addition of a neutralizing antibody to MIP-1 alpha to human bone marrow cultures treated with freshly isolated marrow plasma from patients with MM blocked the increased OCL formation induced by these marrow samples but had no effect on control levels of OCL formation. Thus, high levels of MIP-1 alpha are expressed in marrow samples from patients with MM, but not in marrow from patients with other hematologic disorders or controls, and support an important role for MIP-1 alpha as one of the major factors responsible for the increased OCL stimulatory activity in patients with active MM. (Blood. 2000;96:671-675)
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PMID:Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma. 1088 33

Six-membered peptide fragment TGENHR (HLDF-6) was identified in the HL-60 cell culture of human promyelocyte leukemia treated with retinoic acid when studying the differentiation factor HLDF of this cell line. HLDF-6 retains the ability of the full-size factor to induce the differentiation and arrest the proliferation of the starting HL-60 cells. It was shown that the synthetic peptide HLDF-6 has no specific receptors on the surface of the HL-60 cells but can affect the binding of interleukin IL-1 beta, a cytokine involved in proliferation, to the cell surface. It was found on a model of transplantable NSO myeloma that HLDF-6 has an antitumor activity.
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PMID:[Biologically active fragment of the differentiation factor from HL-60 cell line. Identification and properties]. 1100 40


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