Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abelson murine leukemia virus (A-MuLV)-transformed cells, simian virus 40 (SV40)-transformed cells, and chemically transformed cells all have increased levels of a 50,000-molecular-weight host cell protein. The protein was detected with sera raised to the A-MuLV-transformed and chemically transformed cells and was tightly bound to T-antigen in extracts of SV40-transformed cells. Partial protease digests showed that the proteins from all three sources were indistinguishable. The three proteins were phosphorylated in cells, and the linkage of phosphate to the A-MuLV-associated P50 was to a serine residue. By immunofluorescence methods, P50-related protein was found on the surface of both normal lymphoid cells and A-MuLV-transformed lymphoid cells, but cell fractionation showed that the majority of P50 was free in the cytoplasm of the transformed cells. Immunofluorescence also showed that P50 was found in granules in the cytoplasm of both untransformed and SV40-transformed fibroblasts. Other cells gave indistinct patterns. Cocapping experiments showed that the A-MuLV-specified P120 protein is weakly associated with the surface P50-related protein of lymphoid cells, but no association of P120 and P50 could be demonstrated by immunoprecipitation methods. Although a monoclonal antiserum to P50 was used in many of these studies, the identity of the bulk P50 protein with the molecules that are reactive at the cell surface requires further study.
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PMID:Increased concentration of an apparently identical cellular protein in cells transformed by either Abelson murine leukemia virus or other transforming agents. 626 7

The monoclonal antibody OKT9 reacts specifically with the receptors for transferrin on human cells (Sutherland, D. R., Delia, D., Schneider, C., Newman, R. A., Kemshead, J., and Greaves, M. F. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 4515-4519; in Leukemia Markers (Knapp, W., ed) pp. 157-160, Academic Press, New York) and has been used to isolate and characterize this receptor. The receptor is a dimeric glycoprotein (Mr = 180,000) composed of two subunits (Mr = 90,000) and has a pI of approximately 5.2. The transferrin receptor appears to be a transmembrane molecule and is phosphorylated, the phosphate group being predominantly on serine residues. The cell surface form of the molecular possesses both complex and high mannose oligosaccharide chains, which do not appear to have a direct role in antibody (OKT9) binding. The molecule can be cleaved into a Mr = 70,000 fragment from the cell surface, suggesting that the major part of the receptor is exposed to the extracellular environment. The released Mr = 70,000 fragments are not disulfide-linked and possess the antibody (OKT9)- and transferrin-binding sites. Cross-linking studies using radiolabeled transferrin suggest that two molecules of transferrin are bound to each Mr = 180,000 receptor dimer.
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PMID:Structural features of the cell surface receptor for transferrin that is recognized by the monoclonal antibody OKT9. 628 84

Sera from rat bearing tumors induced by inoculation of FBJ murine osteogenic sarcoma virus (FBJ-MSV) nonproducer rat cells precipitate two proteins with molecular weights of 55,000 (p55) and 39,000 (p39) from FBJ-MSV-transformed cells. These proteins cannot be precipitated from uninfected cells or cells transformed by other strains of murine sarcoma virus, nor can they be precipitated by sera specific for the viral structural proteins. A methionine tryptic peptide mapping analysis showed that p55 and p39 have little or no homology and that they are not related to the helper virus gag and env gene products. p55 could also be detected among the in vitro translation products of 70S RNA from FBJ murine leukemia virus plus FBJ-MSV virions but not among those from FBJ murine leukemia virus alone. This suggests that p55 is encoded by the FBJ-MSV genome, whereas p39, which was not detected among the in vitro translation products, may not be virus encoded. Another difference between p55 and p39 is that p55 is phosphorylated, with most of the phosphate on a serine residue(s), whereas p39 is phosphorylated to a much lesser extent, if at all. No protein kinase activity was associated with p55 and p39 immune complexes under standard conditions. Our data suggest that p55 is a strong candidate for the FBJ-MSV oncogene product.
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PMID:Candidate product of the FBJ murine osteosarcoma virus oncogene: characterization of a 55,000-dalton phosphoprotein. 628 32

The phosphorylation of the high mobility group (HMG) proteins has been investigated in mouse Ehrlich ascites, L1210 and P388 leukemia cells, human colon carcinoma cells (HT-29), and Chinese hamster ovary cells. HMG 14 and 17, but not HMB 1 and 2, were phosphorylated in the nuclei of all cell lines with a serine being the site of modification for both proteins in Ehrlich ascites cells. Phosphorylation of HMG 14 and 17 was greatly reduced in cultured cells at plateau phase in comparison to log phase cells, suggesting that modification of HMG 14 and 17 is growth-associated. However, phosphorylation was not linked to DNA synthesis, since incorporation of 32P did not vary through G1 and S phase in synchronized Chinese hamster ovary cells. Treatment of HT-29 or Ehrlich ascites cells with sodium butyrate reduced HMG phosphorylation by 30 and 70%, respectively. The distribution of the phosphorylated HMG proteins in chromatin was examined using micrococcal nuclease and DNase I. 32P-HMG 14 and 17 were preferentially associated with micrococcal nuclease-sensitive regions as demonstrated by the release of a substantial fraction of the phosphorylated forms of these proteins under conditions which solubilized less than 3% of the DNA. Short digestions with DNase I did not show a marked release of 32P-HMG 14 or 17.
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PMID:The phosphorylation of high mobility group proteins 14 and 17 and their distribution in chromatin. 646 58

We have studied tyrosine phosphorylation in particulate fractions from 11 leukaemic cell lines by using as substrate either a synthetic tyrosine containing peptide or the endogenous proteins. The results were compared with those obtained using similar fractions from normal lymphocytes and bone marrow cells. Particulate fractions from all the leukaemic cell lines and normal bone marrow cells exhibited lower levels of tyrosine protein kinase activity compared to normal lymphocytes. When the phosphorylation of endogenous substrates was assayed, proteins were phosphorylated on tyrosine residues (rather than serine or threonine residues) to a larger extent in normal lymphocytes than in leukaemic cell lines. Separation of labelled endogenous substrates on sodium dodecyl sulfate-polyacrylamide gels showed a number of phosphorylated alkali-resistant bands in the range 14-175kd in the lymphoid cell lines; normal lymphocytes exhibited a smaller number of strongly phosphorylated bands. Normal lymphocytes from different individuals showed reproducible patterns of phosphorylated substrates. Normal bone marrow cells and myeloid leukaemia lines showed weak, if any, phosphorylation. Among the leukaemic cell lines no particular pattern of phosphorylated substrates common to cells of similar phenotype could be detected. We suggest that the level of overall tyrosine protein kinase activity in these fractions reflects their position in the cell cycle rather than their normal or malignant status.
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PMID:Higher tyrosine protein kinase activity in resting lymphocytes than in proliferating normal or leukaemic blood cells. 654 62

A mathematical model of the folic acid cycle and of thymidylate, purines, methionine and serine biosynthetic reactions in leukemia L-1210 and Ehrlich ascite tumour cells was developed. This model was used for an analysis of biochemical criteria of different sensitivity of these tumours to methotrexate, such as differences in the rates of methotrexate transport into the cells, levels of target enzyme, dihydrofolate reductase, its affinity for the inhibitor and the capacity of "salvage" pathways of tetrahydrofolate formation. It was shown that low sensitivity of the Ehrlich ascite tumour cells to methotrexate is due to mainly a high activity of methionine synthetase, which represents a "salvage" pathway of tetrahydrofolic acid regeneration in the presence of methotrexate. The results of this analysis were used to predict a combined utilization of methotrexate and methionine synthetase inhibitor. The pretreatment of the tumour cells of the methionine synthetase inhibitor enhances the effects of methotrexate on the thymidylate and purines syntheses, thus increasing their sensitivity to this drug.
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PMID:[Evaluation of biochemical criteria for sensitivity of tumor cells to methotrexate by means of mathematic simulation]. 676 5

A general description of the folic acid cycle and associate reactions of thymidilate, purines, methionine and serine biosyntheses is presented as a system of differential equations. The concrete models of this reaction complex as well as methotrexate transport into the leukemia L 1210 and Ehrlich ascite tumour cells and the dynamic inhibition of the target enzyme--dihydrofolate reductase--by methotrexate have been described and investigated. The adequacy of mathematical models to the experimental data has been demonstrated.
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PMID:[Mathematical description and study of the folic acid cycle reactions]. 678 26

When maximal effective dose (MED) of BCNU is injected together with liposomes to mice with L-1210 leukemia, the effectiveness of the drug is decreased. But when half the MED is injected with liposomes into such mice, survival is increased compared to mice injected with BCNU alone. Study of liposome composition on BCNU anti-leukemic effect revealed that negatively charged liposomes made of dioleylphosphadyl choline plus phosphatidyl serine given with half the MED of BCNU increased both long-term survival and mean survival time. This enhancement was not produced with negatively charged liposomes made of dioleylphosphatidic acid alone or in liposomes in which phosphatidyl serine plus dioleylphosphatidic acid was diluted with the neutral phospholipid, dioleylphosphatidyl choline.
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PMID:Relative enhancement by various liposomes of BCNU effectiveness against L-1210 leukemia in vivo. 743 63

Some lines of colon cancer cells are forced to undergo differentiation by 12-O-tetradecanoylphorbol-13-acetate (TPA). The increases in activities of both protein tyrosine phosphatase (PTP) and protein tyrosine kinase (PTK) have been reported to be associated with the TPA-induced differentiation of HL-60 leukemia cells. In the present study, a 2-fold increase in PTP activity was observed in SW620 human colon cancer cells after 30 min of TPA treatment; a maximal level (4- to 5-fold) was reached at 60 min and continued for more than 6 hr. In addition, two TPA-induced differentiated characteristics, morphological alteration and release of cellular surface proteoglycan, were effectively blocked by PTP inhibitors, such as sodium orthovanadate (50 microM), zinc chloride (100 microM), and iodoacetate (250 microM), but not by the protein serine/threonine phosphatase inhibitor okadaic acid (20 nM). On the other hand, although TPA induced a transient slight increase in PTK activity (1.4-fold) at 60 min, four PTK inhibitors (genistein, herbimycin A, tyrphostin-23 and quercetin) had different effects on the TPA-induced release of cell surface proteoglycan. Genistein (60 microM) potentiated this process, but in contrast, quercetin (45 microM) could partially inhibit the TPA effect. Taken together, these observations suggest that both PTP and PTK activities were increased in SW620 cells in response to TPA; however, the activation of PTP seems to be preferentially required for the TPA-induced differentiation of SW620 human colon cancer cells.
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PMID:Preferential requirement for protein tyrosine phosphatase activity in the 12-O-tetradecanoylphorbol-13-acetate-induced differentiation of human colon cancer cells. 748 37

Lysis of target cells (TC) by cytolytic lymphocytes involves the secretion of cytoplasmic granules containing perforin and serine esterases by the effector cell (EC). Recently, a granule-independent cytolytic mechanism involving the interaction of the apoptosis-triggering Fas antigen (CD95) with Fas ligand (FasL) has been revealed in T cells. However, whether the Fas lytic pathway also functions in NK cells has not been established. We purified human peripheral NK cells (> 98% CD56+) and found that PMA and ionomycin treatment upregulated FasL message and stimulated the NK cells to lyse a Fas+ TC. This lysis was partially inhibited by the anti-Fas-blocking antibody M3 or by Fas.Fc fusion protein. We also found that FasL is constitutively expressed on the human NK-like leukemia cell line YT-INDY and that YT-INDY utilizes a Ca(2+)-independent Fas lytic pathway, as well as the granule pathway. We have previously shown that CD28/B7 interactions are involved in TC recognition by YT-INDY. K562 cotransfected with Fas and B7-1 (K562/Fas/B7) was lysed by YT-INDY at a higher level than a vector-transfected K562 line, whereas K562 transfected with Fas alone was not. Lysis of K562/Fas/B7 cotransfectants was partially Fas-mediated, as indicated by the presence of Ca(2+)-independent, M3-inhibitable lysis. Ca(2+)-independent, Fas-mediated lysis of several TC by YT-INDY was inhibited by anti-CD28 antibody. Anti-LFA-1 also inhibited Fas-mediated cytotoxicity in YT-INDY. Thus, fresh human NK cells and the human NK-like cell line YT-INDY are capable of using the Fas lytic pathway. In YT-INDY, CD28/B7 and LFA-1/ICAM interactions appear to influence the Fas lytic pathway.
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PMID:Fas involvement in cytotoxicity mediated by human NK cells. 749 25


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