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)

Electrofocusing patterns of plasma fucosyltransferases provide information concerning marrow status of patients with myeloproliferative disorders. Three enzymes were detected in normal plasmas using an acceptor terminating in the sequence N-acetylglucosamine-galactose. The enzyme which focused at pH 4.7 was elevated during rapid proliferation of myeloid cells, e.g., acute myelogenous leukemias and certain infectious diseases. Activity at pI = 5.1 was decreased in acute myelogenous leukemia patients, and from other observations, appears related to the level of erythropoietic activity. Acceptor studies show this enzyme to be specified by the H gene. A third enzyme focused at pH 5.5 and appeared to be correlated with a later step in granulocytes maturation. Two other plasma fucosyltransferases (pl = 5.6 and 8.3) were detected with a high-molecular-weight acceptor terminating in N-acetylglucosamine. This activity was markedly elevated during regeneration of a normal marrow population during drug-induced remission of acute myelogenous leukemia. Additional isoenzymes were detected, using this acceptor, in plasma of patients with certain solid tumors and multiple myeloma. However, the new isoelectric points observed (pH 6.0, 6.9, and 7.8) suggest these enzymes are probably not derived from hematopoietic tissues.
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PMID:Electrofocusing patterns of fucosyltransferases in plasma of patients with neoplastic disease. 8 96

Pyoderma gangrenosum (PG) has been increasingly reported in association with myeloproliferative disorders. Monoclonal gammaopathy, myeloma, myeloid metaplasia, and polycythemia have all been found in association with PG. Recently, seven cases of PG in association with leukemia have been described: three cases with acute myeloblastic leukemia, two cases with chronic myelogenous leukemia, one case with acute lymphoblastic leukemia, and one case with acute leukemia of either plasma cell or myeloblast origin. To these we add two cases of PG with acute myeloblastic leukemia. These patients often have an atypical clinical presentation for PG, with bullae and relatively superficial involvement obscuring the correct diagnosis.
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PMID:Atypical pyoderma gangrenosum with leukemia. 27 73

Four patients with multiple myeloma in whom a Ph1 chromosome was found were described; 1 patient had a (9;22) translocation, 2 had no evidence of a translocation, and 1 had a complex translocation (3;8;22). Ph1 chromosomes with standard (9;22) or with unusual translocations were recently found in various myeloproliferative disorders (other than chronic myelogenous leukemia) and in acute lymphoblastic leukemia. These findings point to the genesis of a Ph1 chromosome in diseases other than chronic myelogenous leukemia and other myeloproliferative disorders.
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PMID:Philadelphia chromosome in human multiple myeloma. 28 21

Factors of the plasma kallikrein system have been evaluated following the course of 48 patients with hematological malignancies which consisted of 15 cases of AML, 6 cases of myeloproliferative disorders, 14 of lymphoproliferative disorders, 8 of multiple myeloma and 5 of bone marrow carcinomatoses. Normal range of spontaneous activity was 11.4 +/- 3.0 micronM/ml TAMe hydrolyzed, kallikreinogen was 115.8 +/- 26.2 micronM/ml.h and enzyme inhibitor was 1.02 +/- 0.37 unit. Lower kallikreinogen level of the range was from 77.2 to 93.1; higher spontaneous activity, 8.4 to 18.0 and lower enzyme inhibitor activity of 0.46 to 0.92 was seen before treatment. Kallikreinogen increased up to the range of 95.6 to 120.1 at complete remission and decreased down to 63.1 - 76.5 prior to death. The causes of the change in these factors were discussed.
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PMID:Kallikrein system during treatment of hematological malignancies. 29 1

Fifty-eight patients with a variety of haematological lymphoproliferative or myeloproliferative disorders were given bivalent subunit influenza virus vaccine, and their antibody responses after vaccination were compared with those of a normal control group. Although geometric mean titres of the patient group showed lower initial antibody levels, smaller increments, and lower final titres, after vaccination 83% of this group achieved satisfactory antibody levels to the A/Pt Chalmers strain, and 57% to the B/Hong Kong strain. The lowest antibody levels and smallest responses occurred in patients with non-Hodgkin's lymphoma, Hodgkin's disease, and multiple myeloma. Four of seven patients who showed low antibody levels, and no response to the first injection, responded to a second dose.
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PMID:Immunization with influenza vaccine in patients with haematological malignant disease. 85 89

Alpha 2-macroglobulin, a major glycoprotein component of plasma, is unique in its capacity to bind and inhibit the proteolytic activities of all classes of proteinases. Since proteinases implicated in cancer dissemination (type-IV collagenase, plasminogen activator, cathepsins B) are normal constitutents of blood, we have explored the hypothesis that elevated tissue levels of activated proteinases bound to alpha 2M might be detected in plasma of patients with cancer. To test this premise, blood was collected from 149 subjects (33 healthy controls, 31 patients with infections and non-malignant diseases, 16 with myeloproliferative disease, 10 with gastrointestinal cancer, 7 with genito-urinary cancer, 16 with lung cancer, 14 with lymphoma, 11 with miscellaneous cancers and 11 with chronic lymphocytic leukemia and myeloma). Plasma was assayed for alpha 2M-proteinase complexes using a sandwich ELISA which employs a mouse monoclonal antibody (MAb) that binds to a neo-antigenic determinant on complexed alpha 2M and a rabbit polyclonal anti-native human alpha 2M antibody. The concentration of complexed alpha 2M in healthy controls was 14.2 +/- 9.8 micrograms/ml (mean +/- standard deviation). No significant differences in complexed alpha 2M were noted between normal and cancer groups (range 7.4-14.6 micrograms/ml). On the basis of these data, we propose that, in patients with cancer, activated proteinases are bound locally to inhibitors in the tissues and are not available to form complexes with plasma alpha 2M. An alternative explanation is that proteinases are not secreted in excess by cancer cells in vivo.
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PMID:Proteinase-alpha 2 macroglobulin complexes are not increased in plasma of patients with cancer. 171 Feb 7

Pyoderma gangrenosum is an uncommon skin disorder characterised by deep ulcers surrounded by a violaceous over-hanging edge. Although in many instances there is no clear association with any underlying disease, pyoderma gangrenosum has been described in ulcerative colitis, Crohn's disease, polyarthritis, diabetes mellitus and myeloma. Pyoderma gangrenosum may also be seen as a rare manifestation of myeloproliferative disease including leukaemia. In children, as in our case, it may be the presenting feature.
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PMID:Pyoderma gangrenosum with large circumferential perianal skin loss in a child. 180 22

Sporadic reports in the medical literature concern the significant incidence of neutrophils with ring-shaped nuclei in myeloproliferative disorders. We report our first encounter with ring neutrophils in patients with lymphoproliferative disorders. A significant incidence of ring neutrophils was observed in all of 20 patients with multiple myeloma and in nine of 10 patients with monoclonal gammopathy of undetermined significance. The mean percent of ring neutrophils was 9.5% (range, 1.0% to 28.0%) in patients with multiple myeloma, which was significantly greater than in those with monoclonal gammopathy of undetermined significance or in healthy controls. In multiple myeloma, the incidence of ring neutrophils in the pretreatment phase was greater than that in the remission phase. A great deal of overlap was noted between multiple myeloma in the remission phase and monoclonal gammopathy of undetermined significance. The incidence of ring neutrophils seemed to vary according to disease stage. Ring neutrophils may reflect abnormal granulopoiesis in plasma cell dyscrasias.
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PMID:Ring neutrophils in plasma cell dyscrasia. 199 87

Interleukin-6 (IL-6) is a multifunctional cytokine involved in the regulation of the terminal differentiation pathway of B lymphocytes. Recent reports revealed its potential role in the in vitro and in vivo growth of human multiple myeloma cells. The mechanism, however, by which IL-6 triggers proliferation of malignant plasma cells remains controversial. Using the very sensitive 7TD 1 bioassay we quantified endogenous circulating IL-6 levels in serum samples of 104 patients suffering from monoclonal gammopathies and other hematological disorders [47 with multiple myeloma (MM), 24 with monoclonal gammopathy of unknown significance (MGUS), 8 with myeloproliferative disease, and 25 suffering from low-grade non-Hodgkin's lymphoma (NHL)]. Elevated serum levels of IL-6 (greater than 5 pg/ml) were detected in 42% of the patients with MM, in 13% with MGUS, in 15% with low-grade B-NHL, and in 1 patient with T-NHL. In patients suffering from chronic myeloproliferative diseases, IL-6 levels were within the normal range. In patients with myeloma, IL-6 levels were significantly higher at advanced stages (II/III) or with progressive disease than in patients with MM stage I, MGUS, or at the plateau phase (P less than 0.01). In patients with monoclonal gammopathies including MGUS, serum IL-6 levels correlated with neopterin, tumor necrosis factor alpha and beta 2-microglobulin. An inverse correlation was found with hemoglobin levels. From these results, we propose that in myeloma patients serum IL-6 levels may reflect disease activity and tumor cell mass. The correlation with serum neopterin, a macrophage product, also suggests its origin in an activated immune system.
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PMID:Serum levels of interleukin-6 in multiple myeloma and other hematological disorders: correlation with disease activity and other prognostic parameters. 203 68

Multiple myeloma (MM) originates from the malignant clonal expansion of transformed B-lymphocytes (in which c-myc and ras oncogenes are probably involved). MM cells have a hybrid phenotype (with coexpression of the markers for both early and late B-differentiation and, sometimes, of T-lymphocyte, myelomonocyte, erythroid and megakaryocyte markers), which accounts for the association between MM and myeloproliferative disorders and for cytokine production. Interleukin-6 and immunologic control mechanisms regulate proliferation and differentiation into plasma cells secreting a monoclonal component (MC). Overt MM is diagnosed 1-2 years following malignant transformation. At this time, several aneuploid clones with resistant phenotype have been selected, and a small pool of actively cycling cells produces the great bulk (over 90%) of non proliferating tumor cells. The clinical and laboratory signs of MM arise from both tumor proliferation and MC damage to organs and organ systems. Tumor proliferation is mainly responsible for bone disease (since MM cells produce cytokines that activate the osteoclasts), inhibition of hemopoiesis and the appearance of plasma cell tumors. The MC causes renal failure, neurological signs, hemorrhagic manifestations. The prognosis for multiple myeloma is probably best estimated by two parameters, serum beta-2-microglobulin and the bone marrow labeling index. Induction therapy is still based on the use of alkylating agents, melphalan and cyclophosphamide, combined with prednisone. Second line treatment consists of VAD polychemotherapy or high-dose pulsed glucocorticoids. Many investigational approaches have been proposed, but their effectiveness awaits confirmation. In the absence of a curative regimen, much effort should be dedicated to the quality of supportive care. In this respect, bisphosphonates represent a new effective tool for the control of myeloma bone disease.
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PMID:Multiple myeloma. 208 Oct 91


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