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)

Several recent studies have demonstrated the presence of specific receptors for the 1,25-dihydroxyvitamin D3 (calcitriol) in activated normal lymphocytes. By DNA cellulose chromatography, we show evidence of such specific receptors in the human myeloma cell line RPMI 8226. Nanomolar concentrations of 1,25-dihydroxyvitamin D3 reduce the proliferation of RPMI 8226 cells significantly and simultaneously induce the appearance of both new properties and phenotype expression, such as butyrate esterase, enhanced expression of CD20 (B1), CD15 (Leu-M1) antigens and lambda chains, and decreased expression of the PC1 antigen using microfluorometric analysis. But such an increased expression of membrane lambda chains was not associated with an enhanced secretion of lambda chains. Furthermore, the bone resorbing activity produced normally by RPMI 8226 cells was reduced significantly after 1,25-dihydroxyvitamin D3 treatment. The possible mechanisms and significance of these new functional and phenotypic properties are discussed with respect to the B-cell lineage.
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PMID:Phenotypic and functional analysis of 1,25-dihydroxyvitamin D3 receptor mediated modulation of the human myeloma cell line RPMI 8226. 283 17

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

Fresh leukaemia cells from the peripheral blood of 6 patients with B-chronic lymphocytic leukaemia (CLL) were cultured in the continuous presence of the phorbolester 12-O-tetradecanoylphorbol 13-acetate (TPA) for in vitro induction of differentiation. Upon treatment with TPA the cells showed distinct morphological changes consisting of cytoplasmic and nuclear enlargement, vacuolisation and protrusion of cytoplasm, eccentric location of nuclei with perinuclear clear zones, and oval to elongated cell forms. Isoenzyme profiles of the enzymes carboxylic esterase, acid phosphatase, hexosaminidase and lactate dehydrogenase (LDH) were analysed by isoelectric focusing on polyacrylamide gels. An increase in the number and in the staining intensity of isoenzymes were observed for all 4 enzymes in the TPA-exposed cells indicating a maturation along the B cell pathway. TPA triggered the new expression of the tartrate-resistant acid phosphatase isoenzyme, a marker of hairy cell leukaemia (HCL) cells, and of the hexosaminidase I isoenzyme, a marker of multiple myeloma cells. The induced phenotypic changes are suggestive of differentiation to stages corresponding to those of HCL cells or 'pre-plasma cells'.
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PMID:Morphological and isoenzymatic differentiation of B-chronic lymphocytic leukaemia cells induced by phorbolester. 348 41

A case of phagocytic, lambda light chain, plasma cell myeloma was characterized by its clinical, morphologic, cytochemical, immunologic, and cell kinetic features. A 40-year-old man presented with Coombs-negative hemolytic anemia, hepatosplenomegaly, lytic bone lesions, lambda light chain monoclonal gammopathy, and infiltration of the bone marrow by dysplastic plasma cells, 10% of which demonstrated phagocytosis of erythroid cells. Electron microscopy demonstrated myeloma cells with prominent cytoplasmic microfilaments and erythroid cells in intracytoplasmic vacuoles. The myeloma cells did not phagocytose staphylococci in vitro. Phagocytic and nonphagocytic myeloma cells were tartrate-sensitive, acid-phosphatase positive, alpha-napthyl butyrate esterase negative, and did not form E rosettes or EAox(IgG) rosettes. The tumor cells were Tdt, Ia antigen, and SIg negative. Immunofluorescent staining for cytoplasmic light chains showed a monoclonal lambda pattern in nonphagocytic myeloma cells, and a probable monoclonal lambda pattern in phagocytic myeloma cells. These findings characterize the neoplasm as a monoclonal proliferation of differentiated plasma cells with the capability of erythrophagocytosis. Erythrophagocytosis by myeloma cells may have been responsible for the hemolytic anemia. The tritiated thymidine labeling index (LI%) was high (8%), suggesting a poor prognosis, despite a dramatic initial response to chemotherapy.
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PMID:Phagocytic, lambda light chain, plasma cell myeloma. 619 Mar 96

The novel aryl phosphate derivative of bromo-methoxy zidovudine (ZDV/AZT) (compound WHI-07, CAS 213982-96-8) was found to be a potent antileukemic agent against human leukemia, lymphoma, and multiple myeloma cell lines in MTT and clonogenic assays with low micromolar IC50 values. In addition, WHI-07 was antimitotic, leading to cell fusion and developmental arrest in the Zebrafish model of rapid cell proliferation. WHI-07 was cytotoxic to drug-sensitive (NALM-6, MOLT-3, HL-60, P388) and multi-drug resistant (MDR) leukemia cell lines (HL-60/VCR, HL-60/ADR, P388/ ADR). Treatment of leukemia cells with WHI-07 showed rapid and dramatic depletion of all cellular nucleoside diphosphate and triphosphate (NDP/NTP) pools, which would contribute to the overall reduction of nucleic acid synthesis and cell death. WHI-07 was rapidly metabolized to alaninyl ZDV monophosphate (Ala-ZDV-MP), the levels of which inversely correlated with cytotoxic IC50 values of WHI-07. Glutathione was found to mediate the in vitro and in vivo detoxification pathway of WHI-07 to 3'-azidothymidine-5'-p-bromophenylmethoxyalaninyl phosphate and Ala-ZDV-MP, respectively. The proposed intracellular metabolic pathway for WHI-07 involves a thiol-mediated dehalogenation step followed by the paraoxon-sensitive carboxylesterase-mediated reaction leading to the formation of Ala-ZDV-MP as the major intracellular metabolite.
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PMID:Antileukemic activity and cellular metabolism of the aryl phosphate derivative of bromo-methoxy zidovudine (compound WHI-07). 1572 64

Multiple myeloma (MM) remains an incurable disease and further development of novel agents is needed. Because constitutive expression of topoisomerase I (TopoI) in MM cells and the efficacy of SN-38, an active metabolite of irinotecan (CPT-11), have been reported, we investigated the therapeutic potential of CPT-11. Of the eight MM cell lines analyzed, four showed 50% inhibitory concentration values of less than 2 microg/mL for CPT-11 and less than 2 ng/mL for SN-38. This efficacy was partly explained by the high expression level of human carboxylesterase-2 (hCE-2) in MM cells. Interestingly, high expression of hCE-2 represented the nature of normal plasma cells, suggesting that hCE-2 could efficiently generate SN-38 within the plasma cells. As expected, higher sensitivity to CPT-11 was observed in hCE-2-overexpressing U266 cells than mock U266 cells. On the other hand, the expression levels of hCE-1, TopoI, UGT1A and ABCG2 did not seem to be associated with the sensitivity of MM cells to CPT-11. In a murine xenograft model inoculated s.c. with RPMI8226 cells, administration of CPT-11 alone significantly reduced the tumor volume. When a combination of CPT-11 and bortezomib was administered, the subcutaneous tumors completely disappeared. Thus, clinical trials on CPT-11 in patients with relapsed or refractory MM are warranted.
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PMID:Overexpression of carboxylesterase-2 results in enhanced efficacy of topoisomerase I inhibitor, irinotecan (CPT-11), for multiple myeloma. 1877 27