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)

The glycerolipids of most cells are characterized by a specific proportion of ether linkages at the sn-1 position of the glycerol backbone. A number of tumors are known to have altered concentrations of ether-linked lipids compared to normal tissues. However, no through examination of the ether-lipid content of human leukemia cells has been reported despite the importance of these lipids in normal leukocyte function. In the present study samples were obtained from adults with acute myelogenous leukemia (AML), chronic granulocytic leukemia in blast crisis, and acute lymphocytic leukemia and from healthy human donors. The cellular lipids were extracted, the individual phospholipid classes were isolated, lipid phosphorus content was determined, and the lipids were converted to diglyceride benzoate derivatives for separation and quantitation of the subclasses by high performance liquid chromatography. The data indicate that all the leukemic cells analyzed have an altered phospholipid composition compared to their respective normal leukocytes. Furthermore, among the AML patients both the percentage of the choline-containing phosphoglyceride fraction (PC) which is alkyl linked and the nmoles alkyl-PC/10(6) cells differ significantly by FAB subtype. A positive correlation between the levels of alkyl-PC and the degree of cellular differentiation is observed. Although no differences are observed between chronic granulocytic leukemia in blast crisis and AML lipids, the leukemic cells contain dramatically lower levels of alkyl-linked PC than do normal polymorphonuclear leukocytes. In contrast, no differences are observed between the alkyl-PC content of normal and leukemic lymphocytes. In light of the relations among ether-lipids, protein kinase C, and cell differentiation, these data suggest the ether-linked lipids are important in myeloid cell function and differentiation.
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PMID:Ether-linked phosphoglyceride content of human leukemia cells. 222 52

The human T-cell leukemia virus type I (HTLV-I) promoter contains three copies of imperfect repeats of a 21-base pair sequence designated here as TRE (Tax-response element) that is responsive to the virally encoded transactivator protein Tax. We have identified and separated four nuclear proteins from C81-66-45 cells, an HTLV-I immortalized Tax-expressing human T-lymphocyte line (Salahuddin et al., 1983), that interact with the TRE-DNA, none of which are identical with the Tax-protein. The proteins identified have molecular weights of about 32, 36 to 42, 50 and 110 kD. Four different methods were used to identify the proteins. First, from different cell lines three or all four of the nuclear proteins were specifically cross-linked by UV irradiation to the radioactively labeled TRE-DNA fragment. Second, TRE-DNA binding proteins sedimented through a glycerol density gradient at rates corresponding to proteins of native molecular weights of 35 to 50 kD and 110 kD. Third, only the 50 kD protein was retained on a biotinylated DNA-streptavidin matrix when the DNA fragment contained the TRE-DNA. Fourth, extensive purification by several cycles of TRE-DNA affinity chromatography resulted in the 32, 36 to 42 and 110 kD proteins and to less extent the 50 kD factor. Two abundant proteins of 75 and 80 kD were competed out by poly[d(I-C)] in all reactions. The cAMP-response element CRE, TGACGTCA, present in the 21 base-pair sequence, appears to be essential for specific protein-TRE-DNA interactions because mutation of the two G's destroys this complex. This result suggests that the cAMP response element binding protein, CREB, is involved in the protein-TRE-DNA complex and in mediating the Tax response.
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PMID:Tax-independent binding of multiple cellular factors to Tax-response element DNA of HTLV-I. 231 99

We studied the effects of the alkyl-lysophospholipid, 1-octadecyl-2-methyl-sn-glycerol-3-phosphocholine (ALP), on human leukemia cells from 56 patients with various leukemias and on normal bone marrow progenitors in order to assess the application of ALP as an in vitro marrow-purging agent. The tumoricidal activity was analyzed by the elimination of clonogenic leukemia cells (leukemic colony-forming cells), by the inhibition of the proliferative capacity [( 3H]thymidine incorporation) of leukemia cells, and by the elimination of viable leukemia cells measured with flow cytometry. The tumoricidal activity of ALP was dose and incubation time related, as, although to a lesser extent, held true for normal marrow progenitors. For some leukemias the ALP dose necessary for the elimination of 100% of the leukemic colony-forming cells is probably too toxic for normal marrow cells. The results of this study strongly support the possibility that ALP is a promising purging agent in the majority of patients with leukemias.
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PMID:Selective killing of malignant cells from leukemic patients by alkyl-lysophospholipid. 235 51

Expression of a region of the Moloney murine leukemia virus (M-MuLV) pol gene in Escherichia coli resulted in the synthesis of reverse transcriptase activity which could be detected in crude extracts. Construction of deletions at the 3' terminus of this gene resulted in a 4-fold increase in the level of the reverse transcriptase activity in the soluble fraction of crude lysates and yielded the high level production of a stable protein species of Mr = 71,000. Purification of this protein by column chromatography on DEAE-cellulose, phosphocellulose, polyribocytidylic acid-agarose, and hydroxylapatite indicated that it was a multifunctional enzyme containing RNase H and reverse transcriptase activity. The Mr = 71,000 species had a sedimentation coefficient of 4.65 S by glycerol gradient centrifugation, indicating that the enzyme was a monomer. Using poly(A)+ mRNAs primed with oligo(dT), the enzyme synthesized double-stranded DNA copies between 1.3 and 9.9 kilobases in length. Synthesis of long cDNA required 8 mM Mg2+, 4 mM Mn2+, 2 mM dNTPs, and saturating levels of enzyme. Actinomycin D efficiently limited the enzyme to the first strand synthesis. Additional characteristics of the fusion protein are described.
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PMID:Purification and characterization of murine retroviral reverse transcriptase expressed in Escherichia coli. 241 Apr 13

The functional role of a mutant RAS gene in immortal myeloid cell proliferation was examined in a fastidious interleukin-3 (IL-3) dependent cell line (NFS/N1.H7) formed by forced proliferation in IL-3 of marrow cells of the NFS/N mouse. The NFS/N1.H7 cell line was strictly dependent upon IL-3 for growth, and the cell line could be activated by phorbol esters (PMA) to augment IL-3 dependent proliferation, but when pKC was downregulated, diminished IL-3 proliferative response resulted. Transfection (electroporation) of the T24 RAS-containing vector pAL8 to NFS/N1.H7 led to clones (H7 NeoRas.F3, H7 NeoRas.E2) that had incorporated the entire 6.6 Kb human mutant H-RAS genome. The mutant RAS-containing clones demonstrated greater proliferation than parent cells or cells containing a control (neo-resistance) vector over a range of suboptimal IL-3 does and in optimal IL-3 concentrations had a faster doubling rate than parent cells. The clone H7 NeoRas.F3 was studied biochemically, and found to constitutively form 3-fold more 3H-diacylglycerol than the parent cell line upon exposure to 3H-glycerol. PMA could partially repair the proliferative defect of NFS/N1.H7 compared to the RAS-expressor. These studies affirm a secondary, accelerating role for a mutant RAS gene product acting through pKC to promote clonal expansion of immortal myeloid cells stimulated by IL-3.
Leukemia 1989 Sep
PMID:A mutant RAS gene acts through protein kinase C to augment interleukin-3 dependent proliferation in a fastidious immortal myeloid cell line. 266 57

A number of synthetic ether-linked phospholipids are selectively cytotoxic to neoplastic cells. However, the mechanisms underlying this selective cytotoxicity are not known. We have investigated the ether-lipid content of HL-60 and K562 human leukemia cells in relation to their sensitivity to 1-O-alkyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3). HL-60 cells are much more sensitive than K562 cells to the cytotoxic effects of ET-18-OCH3 and, at the same time, they contain nearly twice as much ether lipid as the more resistant K562 cells. These observations suggested a relation between the cellular ether-lipid content and sensitivity to ET-18-OCH3. Further evidence linking these properties was obtained when the ether-lipid content of K562 cells was increased by incubating them in medium containing 1-O-hexadecyl-sn-glycerol. This supplementation not only increased the ether-lipid content of the cells but also increased their sensitivity to ET-18-OCH3. The 50% inhibitory concentration for ET-18-OCH3 decreased from 18.4 microM in the control cells to 9.83 microM in the supplemented cells.
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PMID:Correlation of ether lipid content of human leukemia cell lines and their susceptibility to 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine. 274 33

Changes in the production of reactive oxygen species and total superoxide dismutase activity have been observed during differentiation of some hematopoietic cells. We therefore investigated whether the steady-state level and rate of transcription of superoxide dismutase-1 (SOD-1) mRNA change during terminal differentiation of the human leukemia cell lines THP-1, HEL, and HL-60 into macrophages and/or granulocytes, respectively. Macrophage differentiation is accompanied by a gradual decrease in both the transcription rate (10x) and the steady-state level (6x) of SOD-1 mRNA. No decrease was observed after treatment with the diacylglycerol analog 1,2 dioctanol-rac-glycerol (di-C8), which like phorbol 12-myristate 13-acetate also activates protein kinase C but does not induce differentiation at the concentration used. The same decrease in SOD-1 mRNA level was observed when HL-60 cells were induced to differentiate into granulocytes by treatment with dimethylsulfoxide. These data suggest that a decrease in SOD-1 mRNA to almost undetectable levels accompanies differentiation of macrophages and granulocytes.
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PMID:Loss of copper-zinc superoxide dismutase gene expression in differentiated cells of myelo-monocytic origin. 279 Feb 4

Phorbol-12,13-dibutyrate (PDBU), a tumor-promoting and protein kinase C-activating phorbol ester, inhibited formylmethionylleucyl-phenylalanine-induced generation of inositol mono-, bis-, and tris-phosphates from the hydrolysis of phosphoinositides in human leukemia (HL-60) cells, which had been differentiated to polymorphonuclear leukocyte-like cells by pretreatment with dibutyryl cyclic adenosine 3':5'-monophosphate. PDBU did not alter the binding of formylmethionylleucyl-phenylalanine to the cells. Other protein kinase C-activating substances such as 12-O-tetradecanoylphorbol-13-acetate and 1-oleoyl-2-acetyl-glycerol could substitute for PDBU, but 4 alpha-phorbol-12,13-didecanoate, which is inactive for both tumor promotion and protein kinase C activation, was ineffective in this capacity. Prolonged treatment of the cells with PDBU resulted in the down-regulation and decrease of protein kinase C activity to the level of 30-40% of that in the control cells. In the down-regulated cells, formylmethionylleucylphenylalanine still induced generation of the phosphorylated inositols to the same extent as that in the control cells, but the inhibition of this reaction by PDBU was reduced to 30-50% as compared with that in the control cells. These results strongly suggest that tumor-promoting phorbol esters inhibit the agonist-induced phosphoinositide hydrolysis through the activation of protein kinase C in the differentiated HL-60 cells.
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PMID:Inhibition of chemotactic peptide-induced phosphoinositide hydrolysis by phorbol esters through the activation of protein kinase C in differentiated human leukemia (HL-60) cells. 301 Dec 48

Phosphorylation of a 36,000-dalton (36k-Da) protein of rat basophilic leukemia (RBL-2H3) cell membranes was investigated. This phosphoprotein has been suggested to be the beta-subunit protein of the immunogloblin E (IgE) receptor of RBL-2H3 cells [Teshima et al., Biochem. biophys. Res. Commun. 125, 867-874 (1984)]. Phospholipids such as phosphatidyl serine, phosphatidyl inositol and phosphatidyl ethanolamine, which are known to be activators of protein kinase C, enhanced the phosphorylation of the 36K-Da protein. In contrast, 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H-7) which has been identified as a potent inhibitor of protein kinase C in vitro decreased incorporation of radioactive phosphate from [gamma-32P]ATP into this protein. These results indicate that the phosphorylation of the 36K-Da protein of RBL-2H3 cell membranes is catalyzed by protein kinase C. H-7 also inhibited the release of serotonin from RBL-2H3 cells stimulated with an antigen or calcium ionophore A23187 and 12-O-tetradecanoyl phorbol 13-acetate (TPA). Treatment of the antigen-stimulated cells with TPA caused a synergistic effect on the serotonin release. A similar effect was obtained by treatment of A23187-stimulated cells with TPA or 1-oleoyl-2-acetyl glycerol.
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PMID:Possible involvement of phosphorylation of a 36,000-dalton protein of rat basophilic leukemia (RBL-2H3) cell membranes in serotonin release. 308 12

The role of liposome entrapment in modulating the cytotoxicity of a lipophilic cisplatin derivative was assessed. cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum++ +(II) (NDDP) was tested in suspension (free NDDP) or entrapped in multilamellar vesicles composed of dimyristoylphosphatidyl choline and dimyristoylphosphatidyl glycerol (L-NDDP). Against LoVo colon carcinoma cells sensitive to cisplatin, L-NDDP was two times more cytotoxic in vitro than free NDDP and cisplatin (Do 7 microM for L-NDDP, 15 microM for free NDDP, and 16 microM for cisplatin). Against LoVo cells resistant to a concentration of 3 micrograms/ml of cisplatin, L-NDDP was three times more cytotoxic than free NDDP and cisplatin (Do 14 microM for L-NDDP, 45 microM for free NDDP, and 48 microM for cisplatin). In in vivo studies, free NDDP was less potent and less active than L-NDDP against i.p. L-1210 leukemia (free NDDP, optimum %T/C 148 at a dose of 75 mg/kg; L-NDDP, optimum %T/C 185 at a dose of 25 mg/kg) and i.p. L1210/PDD leukemia (free NDDP, optimum %T/C 128 at a dose of 50 mg/kg on Days 1, 5, and 9; L-NDDP, optimum %T/C 200 at a dose of 12.5 mg/kg on Days 1, 5, and 9). Free NDDP administered i.v. was inactive against liver metastases of M5076 reticulosarcoma (%T/C 102) while L-NDDP showed significant activity (%T/C 140). The single dose i.v. LD50 in mice of free NDDP and L-NDDP were similar (79.4 mg/kg for free NDDP and 64.5 mg/kg for L-NDDP). These studies show that NDDP is a liposome-dependent drug since it can only be satisfactorily formulated in the liposomal form and since the liposomal carrier plays a crucial role in determining its antitumor activity.
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PMID:Increased cytotoxicity and reversal of resistance to cis-diamminedichloro-platinum(II) with entrapment of cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum (II) in multilamellar lipid vesicles. 339 3


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