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)

A patient with multiple myeloma, IgG kappa type, developed erythroleukemia with cytogenetic abnormalities three years after diagnosis. The latter disease progressed terminally to acute granulocytic leukemia. Anti-idiotype antibody reagents were prepared by injecting rabbits with the purified monoclonal IgG kappa obtained from the patient's serum and subsequent absorption of the antisera with normal IgG coupled to Sepharose 4B. These reagents reacted specifically with autologous myeloma cells but failed to react with all tested allogeneic cells: these included myeloma cells, reactive lymphocytes and plasma cells, and established lymphoid cell lines. Common idiotypic determinants were found in lymphoid and plasmacytic cells of the patient's marrow, spleen, lymph node, and gastrointestinal tract at autopsy that were not present in the leukemic population. The findings indicate that myeloma and granulocytic leukemia cells have separate clonal origins.
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PMID:Idiotype in myeloma terminating in erythroleukemia. 12 Nov 48

Among 246 patients (49 with Hodgkin's disease, 29 with multiple myeloma, 75 with other lympho- and immunoproliferative syndromes, 70 with carcinomas and 23 with non-malignant affections) treated by cytostatic or immunosuppressive chemotherapy, 6 developed malignant hemopathy (acute myeloblastic leukemia, erythroleukemia and erythremia) apparently induced during the last 7 1/2 years. In addition, 2 carcinomas have been noted. All have received melphalan or chlorambucil, alone or associated with other cytostatic drugs. 5 out of these 6 patients also underwent radiotherapy. The lenght of chemotherapy ranged between 7 and 110 months and the latency between 45 and 110 months. A "preleukemic" cytopenia phase was observed in 4 out of 6 cases. An exceptional 45-month survival was secured in case 1 (acute myeloblastic leukemia in a patient probably cured of Hodgkin's disease IIIB). Observation 2 is the 3rd case ever published of induced acute leukemia in disseminated lupus erythematosus. All these observations are compared with the latest findings in the literature. To the very extent that the utilization of cytostatic drugs produces improvement in the prognosis of very serious diseases, their leukemogenic potential becomes more dangerous and demands limitation of their use.
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PMID:[Induced malignant hemopathies. 6 new cases with 1 patient surviving 45 months]. 28 15

Ionizing radiation used for diagnosis or therapy has been associated with an increased incidence of malignancies of blood-forming organs. The increased incidence of hematopoietic malignancies following exposure to ionizing radiation obtained in the course of occupation, diagnosis and therapy of disease, or as a weapon of war is documented. The natural occurrence and the induced progression to acute leukemia of polycythemia rubra vera, Hodgkin's disease, multiple myeloma, Di Guglielmo's disease, and reticuloendothelial malignancies are discussed. The status of transplantation and immunodeficiency states and their relationship to acute leukemia is reviewed. Finally, drugs, toxins, and the use of cytotoxic radiomimetic agents for nonmalignant purposes are shown to lead to the development of acute leukemia. Background information relevant to the proper use of future diagnostic and therapeutic modalities is provided.
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PMID:Malignancies in blood-forming organs following diagnostic and therapeutic procedures: a review. 106 32

Modulation of the expression of P-glycoprotein, a plasma membrane protein associated with multidrug resistance, was examined in drug-sensitive and drug-resistant tumor cells treated with leukoregulin, a M(r) 50,000 cytokine from human lymphocytes that rapidly permeabilizes the plasma membrane of many tumor cells facilitating the uptake of doxorubicin and other tumor-inhibitory antibiotics. P-glycoprotein expression was measured flow cytometrically by the binding of C219 or MRK16 monoclonal antibody to multidrug-sensitive human K562 erythroleukemia and 8226/S myeloma cells, compared to multidrug-resistant 8226/DOX40 myeloma cells. Cells were treated for up to 2 h with up to 80 units of leukoregulin/ml or one of a variety of unrelated cytokines including interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, colony-stimulating factor, macrophage colony-stimulating factor, granulocyte macrophage colony-stimulating factor, tumor necrosis factor alpha, gamma-interferon, alpha-interferon, epidermal growth factor, platelet-derived growth factor AA, platelet-derived growth factor BB, insulin-like growth factor I, insulin-like growth factor II, fibroblast growth factor, or transforming growth factor beta. Leukoregulin caused a concentration-dependent decrease in P-glycoprotein expression; however, P-glycoprotein expression was unaffected by the other cytokines (< 12% decrease in expression). Leukoregulin-induced membrane permeabilization, determined flow cytometrically by intracellular fluorescein efflux, and decreased P-glycoprotein expression occurred simultaneously within 15 min in drug-sensitive and -resistant cells. Enhanced doxorubicin uptake, measured flow cytometrically by doxorubicin influx, was also present within 15 min. Leukoregulin enhancement of doxorubicin uptake and increased membrane permeability varied directly with the decrease in P-glycoprotein expression. Leukoregulin in combination with doxorubicin enhanced the inhibition of cell proliferation in 8226/DOX40 multidrug-resistant cells over expressing P-glycoprotein. In contrast, combined treatment of HL-60/MX2 multidrug-resistant human promyelocytic leukemia cells that do not overexpress P-glycoprotein in association with their multidrug resistance resulted in no greater growth inhibition than observed with HL-60/MX2 cells treated with doxorubicin alone. This is the first demonstration that a naturally occurring macromolecule with anticancer activities can modulate the expression of P-glycoprotein concomitant with enhanced drug uptake and inhibition of cell proliferation.
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PMID:Decreased P-glycoprotein expression in multidrug-sensitive and -resistant human myeloma cells induced by the cytokine leukoregulin. 135 22

Actinobacillus actinomycetemcomitans produces a cytolytic peptide leukotoxin which kills susceptible target cells, including human neutrophils, monocytes, lymphocytes, and HL-60 promyelocytic leukemia cells. Cell death occurs as a consequence of colloid osmotic lysis. In the present investigation early leukotoxin-induced changes in membrane permeability were studied by flow cytometry and quantitative spectrofluorimetry in leukotoxin-susceptible and resistant targets. Within 5 s toxin-susceptible cells exhibited concentration-dependent, sustained increases in systolic free Ca2+, and this was rapidly followed by a progressive fall in membrane potential. These early manifestations of membrane injury occurred approximately 10-15 min before cell death, as reflected by flow cytometric analysis of propidium iodide stained cells. The rise in cytosolic Ca2+ was almost entirely due to an influx of extracellular Ca2+. The results of Hill plots for the action of leukotoxin on Ca2+ permeability in human neutrophils or HL-60 cells suggested that two or more toxin molecules participate in the assembly of an ion conducting pore in the plasma membrane. Changes in membrane permeability or cell viability were not observed in response to heat-inactivated toxin. Under appropriate conditions toxin-induced membrane abnormalities were inhibited by leukotoxin-neutralizing mAb or relatively high concentrations (greater than or equal to 2.5 mM) of extracellular Ca2+. Leukotoxin-resistant target cells showed no evidence of membrane injury even when exposed to high concentrations of leukotoxin for prolonged periods of time. These included resistant human K562 erythroleukemia cells and murine SP2 myeloma cells which have previously been shown to adsorb the toxin, suggesting that they possess a protective mechanism(s) which impedes toxin insertion or assembly in the lipid bilayer. These data support the concept that A. actinomycetemcomitans leukotoxin acts as a cell-specific, pore-forming protein which permeabilizes the plasma membrane of susceptible target cells.
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PMID:Early changes in cytosolic calcium and membrane potential induced by Actinobacillus actinomycetemcomitans leukotoxin in susceptible and resistant target cells. 194 Mar 58

Synthesis of alpha- and beta-globin RNA in DMSO-induced Friend's erythroleukemia cells and synthesis of immunoglobulin gamma- and kappa-chain RNA, total RNA, 5S RNA, and tRNA in mouse myeloma cells (MPC-11) was inhibited by gamma-irradiation. For all RNA species, synthesis decreased nearly exponentially as a function of radiation dose, whereas RNA size distributions, turnover rates, and specific activities of radioactively labeled RNA were affected only insignificantly. D37 values for the loss of synthesis of various RNA species correspond to target sizes ranging from 21,000 to 53,000 kd, or 30-80 kbp of DNA. These target sizes are several-fold larger than the structural genes in question; however, they correspond well with the size of DNA loops, or "domains" constrained by the nuclear matrix. The data suggest that the eukaryotic transcription unit is the torsionally constrained chromatin loop, transcription of which may be inactivated, or significantly reduced by a DNA single-strand break.
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PMID:Structure of transcriptionally active chromatin: radiological evidence for requirement of torsionally constrained DNA. 247 70

A monoclonal antibody (MoAb) H229(IgGl) was obtained by fusion between SP2/0, mouse myeloma cell line and spleen cells from BC3Fl mice immunized with HEL, a erythroleukemia cell line. MoAb H229 precipitated a 55 kilodalton(KD) molecule in reduced condition. It reacted with platelets and megakaryocytes, but not with monocytes, granulocytes, lymphocytes, thymocytes, red blood cells (RBC), colony-forming units-granulocyte/monocyte (CFU-GM), and burst forming units- erythroid (BFU-E). These findings suggest that MoAb H229 reacts with platelets specifically. However, MoAb H229 did not inhibit platelet aggregation induced by ristocetin, ADP, epinephrine and collagen.
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PMID:A monoclonal anti-platelet antibody which recognizes p55 antigen. 275 47

A case of secondary erythroleukemia treated with apparent success with androgen is reported. The patient is 63-year-old Japanese female. She had a history of multiple myeloma and had been treated with melphalan, vincristine and prednisolone. She developed erythroleukemia 88 months after the initiation of chemotherapy, while her myeloma was a complete remission. She was treated first with vitamin D3 with no beneficial effect and subsequently with 0.5 mg/kg of mepitiostane. A hematologic improvement began two months from the initiation of androgen therapy, and a complete remission of erythroleukemia was attained thereafter. A chromosomal abnormality of bone marrow cells, which was observed at the time of developing erythroleukemia, also disappeared after the treatment. She remained in good condition and hematologic remission under the androgen therapy at the latest follow-up, 1-year after the development of erythroleukemia. Androgen therapy may be considered as a useful treatment for secondary erythroleukemia.
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PMID:[Successful treatment of secondary erythroleukemia with androgen]. 281 Jul 94

The isoenzyme patterns of carboxylic esterase (E.C. 3.1.1.1) were studied in 74 proven human leukemia-lymphoma and 12 normal B-lymphoblastoid cell lines. These cell lines have been extensively phenotyped using poly- and monoclonal antibodies. Esterase isoenzymes were separated by isoelectric focusing and visualized by histo-cytochemical techniques. No leukemia-specific or (except for monocytes) blood cell type-specific isoenzyme or isoenzyme pattern could be detected. The monocytic element in some cell lines was characterized by a strong isoenzyme band which could be selectively and completely inhibited by sodium fluoride. The enzyme phenotypes were stably expressed in all subcultures of a given cell line and did not appear to have any cell cycle dependency. The leukemia-lymphoma cell lines have been subclassified into four major groups according to immunological parameters: T-cell, B-cell, myelomonocytic and non-T, non-B-cell. On the basis of immunological data the T-cell lines were assigned to five stages of differentiation. The number and staining intensity of the isoenzymes increased with differentiation of the T-cells paralleling the expression of immunological markers. The B-cell leukemia-lymphoma cell lines were divided into pre B-, B-, Burkitt lymphoma, multiple myeloma and hairy cell leukemia cell lines. Substantial variability among the isoenzyme patterns was detected ranging from immature profiles of pre B-cell lines to complete isoenzyme repertoires of multiple myeloma cell lines. No significant difference was seen between the isoenzymes of mature B-cell lines and normal B-lymphoblastoid cell lines. The most prominent feature seen in myelomonocytic cell lines was the monocytic band indicating a monocytic origin and separating the 'monocytoid' from the 'pure myeloid' cell lines. Considerable heterogeneity in the isoenzyme patterns was observed in the non-T, non-B cell groups which comprised erythroleukemia cell lines and cell lines arrested at a very early stage of lymphoid differentiation. These latter cell lines together with some T- and B-cell lines shared the common characteristics of positivity for cALLA, TdT and Ia antigens and an immature, incomplete isoenzyme profile. The results support the notions of maturation arrest and normal gene expression in leukemic cell populations. Furthermore, the importance of biochemical studies as part of the multiple marker analysis could be demonstrated.
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PMID:Isoenzyme studies in human leukemia-lymphoma cell lines--1. Carboxylic esterase. 298 79

A new method was developed to study transient gene expression, stable transformation, and cotransformation in suspension cells, such as mouse myeloma and erythroleukemia cells. This method involves attachment of cells to a concanavalin A-coated tissue culture dish, treatment of cells with DEAE-dextran to adsorb plasmid DNA to the attached cells, and finally treatment with a 40% solution of polyethylene glycol to facilitate the uptake of DNA by the cells. Plasmids pSV2cat and pSV2neo were used as markers to optimize the conditions for transient gene expression and stable transformation, respectively, of mouse myeloma and erythroleukemia cells. This method was successfully used to obtain cotransformants of mouse myeloma cells.
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PMID:Gene transfer method for transient gene expression, stable transformation, and cotransformation of suspension cell cultures. 298 79


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