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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine erythroleukemia cells, grown in culture and induced to differentiate by dimethylsulfoxide (DMSO), were employed to explore the relationship between cellular proliferation and maturation. The expression of an erythroid phenotype, as measured by the accumulation of hemoglobin, occurred over a narrow range of concentrations of inducers; the maximum degree of differentiation was attained at a level of inducing agent which caused slight inhibition of cell replication. Stationary phase cells with diminished capacity for DNA synthesis failed to differentiate in the presence of DMSO; whereas, in contrast, exponentially growing murine leukemia cells undergoing extensive DNA biosynthesis readily attained a differentiated phenotype. The induced synthesis of hemoglobin in Friend cells exposed to DMSO was inhibited by 5-bromo-2'-deoxyuridine, arabinosylcytosine and hydroxyurea, when cells were simultaneously exposed to DMSO and a metabolic inhibitor. However, addition of either 5-bromo-2'-deoxyuridine, arabinosylcytosine or hydroxyurea to cultures pretreated with DMSO did not prevent the ultimate expression of the erythroid phenotype. These findings suggest that a process which is associated with cellular proliferation is required for the initiation of murine erythroleukemia cell maturation, but not for the ultimate accumulation of the erythroid marker hemoglobin in cells programmed to differentiate.
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PMID:Relationship between cellular replication and erythroid differentiation of murine leukemia cells. 722 97

The effects of low doses (40 to 1000 units/ml) of mouse interferon (IF) on the expression of Friend leukaemia virus (FLV) and globin genes in Friend leukaemia cells (FLC) have been examined. IF blocks production of extracellular virus, but virus antigens accumulate in the cytoplasm. In cells treated with IF at the time of seeding, there is a reduction in the amount of RNA specified by the lymphatic leukaemia virus (LLV) component of FLV; with the same IF dose there is a small but definite stimulation of haemoglobin and globin mRNA synthesis. The effects of IF on LLV gene expression are even more pronounced in dimethyl sulphoxide (DMSO)-stimulated LFC. No correlation was found between LLV gene expression and the appearance of erythroid markers.
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PMID:Interferon effects on Friend leukaemia cells. I. EXpression of virus and erythroid markers in untreated and dimethyl sulphoxide-treated cells. 735 33

Several phorbol esters, the potent tumour-promoting agents isolated from croton oil, induce proliferation of human lymphocytes and enhance the mitogenic effect of lectins on bovine lymphocytes. While studying the mitogenic properties of one of these agents, phorbol myristate acetate (PMA), we found that dimethyl sulphoxide (DMSO), frequently used as a solvent for PMA, markedly inhibits PMA-induced mitogenesis at DMSO concentrations that have little effect on phytohaemagglutinin (PHA)-induced responses. DMSO, as well as a variety of other organic compounds, induce erythroid differentiation in Friend leukaemia (FL) cells. Phorbol esters, on the other hand, are potent inhibitors of both spontaneous and induced cellular differentiation. We therefore investigated the relationship between the potency of compounds to induce erythroid differentiation in FL cells and their potency to inhibit lymphocyte proliferation induced by PMA and other mitogens. We report here that many of the compounds that induce erythroid differentiation in FL cells are similar to DMSO in selectively suppressing PMA-induced lymphocyte mitogenesis.
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PMID:Chemical inducers of differentiation in Friend leukaemia cells inhibit lymphocyte mitogenesis. 737 56

This study has determined the effects of phorbol-12-myristate-13-acetate (PMA) and dimethylsulfoxide (DMSO) on mRNA levels for the serglycin proteoglycan core protein in human erythroleukemia (HEL) cells. We have compared these changes to those for mRNA for other proteins which are known to be synthesized by HEL cells and megakaryocytes and are known to be localized to alpha granules within platelets. PMA caused a large increase in mRNA for serglycin within two hours of treatment of the cells, and the increase persisted for at least 72 hours. DMSO did not cause a significant change in mRNA levels. mRNA for platelet factor 4, transforming growth factor-beta, and P-Selectin (PADGEM, GMP-140) were also increased by PMA treatment. The mRNA for platelet factor 4 was substantially reduced in the presence of DMSO. The increase of mRNA for serglycin induced by PMA was consistent with our previous observation that synthesis of proteoglycans from [35S]sulfate was greatly stimulated by PMA in HEL cells. The data suggest that up-regulation of synthesis of proteoglycans is induced by PMA in cells which have the capacity to differentiate along the megakaryocytic lineage, as opposed to cell lines such as HL-60 in which proteoglycan synthesis is reduced in the presence of this differentiation-inducing agent.
Leukemia 1993 Dec
PMID:Expression of mRNA for serglycin core protein and other platelet alpha granule proteins is increased in human erythroleukemia cells by phorbol myristate acetate. 750 70

It has been reported that human promyelocytic leukemic HL-60 cells which undergo differentiation fail to respond by apoptosis when treated with antitumor drugs, predominantly DNA topoisomerase inhibitors. Because S phase cells are selectively sensitive to these drugs, and during differentiation there is a reduction in the proportion of cells in S phase, the reported decrease in the number of apoptotic cells could simply be a reflection of the paucity of sensitive cells in these cultures. Using cytometric methods which allow apoptosis to be related to cell cycle position, we have compared the apoptotic response of HL-60 cells growing exponentially and induced to myeloid differentiation by dimethyl sulfoxide (DMSO). The cells were treated with: (i) the DNA topoisomerase I inhibitor camptothecin (CAM), which selectively triggers apoptosis or S phase cells; (ii) the nucleoside antimetabolite 5-azacytidine (AZC) and hyperthermia, both of which preferentially affects G1 cells; and (iii) gamma radiation, which causes apoptosis predominantly of G2 + M cells. The cells exposed to 1.4% DMSO for 24 or 48 h were significantly more resistant to response by apoptosis, regardless of the nature of the agent and regardless of their position in the cell cycle. Thus, induction of differentiation lowers the cell's ability to respond to a variety of damaging agents by apoptosis and this effect is not correlated with cell cycle position. In addition, the difference in response was unrelated to expression of the apoptosis-modulating protein bcl-2, which appeared unchanged following 48 h exposure to DMSO. On the other hand, when the cells were pretreated with low concentrations of CAM or AZC, washed free of drug, and then treated with DMSO, the proportion of cells undergoing apoptosis was markedly increased, relative to drug-treated cells returned to DMSO-free medium. The present data may indicate that while the drug-induced damage screening mechanisms, which are linked to triggering apoptosis, may be more proficient in proliferating cells, the effectors of apoptosis are more expressed in cells undergoing differentiation. The data also suggest that the efficiency of chemotherapeutic agents or radiation may be reduced if a differentiating agent is used in combination therapy and is administered first. An enhancement of apoptosis, however, may be expected if the differentiating drug is administered in the reverse sequence.
Leukemia 1994 Feb
PMID:Altered susceptibility of differentiating HL-60 cells to apoptosis induced by antitumor drugs. 750 35

The activity of the octapeptide pyroGlu-Asp-Asp-Ser-Asp-Glu-Glu-Asn in the control of cell growth and differentiation of human myeloblastic leukemia cells HL-60 is reported. Treatment with peptide slightly slows down the rate of cellular proliferation and this effect becomes more evident in cells grown for several weeks in the presence of the effector. An enhanced effect (40-50% inhibition respect to the control) is found in reversibly permeabilized cells and after 1% DMSO is added to the medium. Moreover the presence of peptide markedly increases the percentage of cells differentiated by DMSO and RA. The effect in DMSO-induced cells is more evident than that observed in RA-induced cells. This in agreement with our hypothesis that DMSO facilitates the peptide entry and its effect is due to an intracellular action.
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PMID:Synthetic octapeptide pyroGlu-Asp-Asp-Ser-Asp-Glu-Glu-Asn promotes differentiation in promyelocytic HL-60 cell line. 754 88

Gene therapy is a potential treatment for hemophilia, wherein cells transduced with a normal factor IX gene could provide a continuous in vivo source of circulating factor IX. In this study, we examined the potential use of hematopoietic cells as a target for factor IX gene therapy. Human myeloid leukemia cells (HL-60) were transduced by retroviral vectors carrying a normal human factor IX cDNA under control of either the Moloney murine leukemia virus long terminal repeat (MoMuLV LTR) (LIXSN), the SV40 promoter (LNSVIX), or a cytomegalovirus (CMV) promoter (LNCIX). Factor IX production was measured in the transduced cells both in the uninduced state and after induction of granulocytic differentiation [with dimethylsulfoxide (DMSO)] or monocytoid differentiation [with phorbol myristic acetate (PMA)]. Transcription of factor IX from the MoMuLV LTR was seen in all cells, with a two-fold increase upon differentiation. Induction with PMA led to an 8- to 15-fold increase in factor IX transcripts from an internal CMV promoter. No factor IX transcripts from the internal SV40 promoter were detected. Immunoreactive factor IX protein was identified by Western blot from induced HL-60 cells transduced by either LIXSN or LNCIX. Factor IX production by HL-60 cells transduced by LNCIX ranged from 38-93 ng/10(6) cells/24 hr following induction of monocytic differentiation. The factor IX antigen titer was directly related to factor IX coagulant titer (r = 0.98; p < 0.001). These data indicate that human myelomonocytic cells are capable of performing the necessary post-translational modifications to produce functional factor IX.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of biologically active human factor IX in human hematopoietic cells after retroviral vector-mediated gene transduction. 757 6

Myeloperoxidase (MPO) is a microbicidal protein present in the primary granules of myeloid cells. Transcription of the MPO gene is turned on only during the late myeloblast and promyelocyte stages of myeloid maturation. Identification of cis-regulatory elements and transcription factors which regulate the MPO gene should, therefore, shed light on myeloid maturation. We report transfection and in vitro transcription experiments which demonstrate promoter activity in the proximal 5'-flanking region of the human MPO gene. Using a chloramphenicol acetyl transferase (CAT) reporter vector system, and segments of the 5'-flanking MPO DNA, we constructed a series of MPO promoter-CAT expression vectors. By electroporation and lipofectin-mediated transient transfection assays, as well as by in vitro transcription studies, a 594-bp MPO DNA sequence (bp -583 to +11) showed promoter activity in a variety of MPO-expressing and non-MPO-expressing cell lines. Compared with the SV40 early promoter, the MPO promoter had greater relative activity in MPO-expressing than in non-MPO-expressing cell lines, suggesting slight tissue specificity. However, a CAT reporter plasmid containing 1099-bp of 5'-flanking MPO DNA showed greater specificity for MPO expressing cell lines. Analysis of a group of promoter deletion mutants showed that the minimal promoter was contained in a DNA fragment extending from bp-128 to +11. The remainder of the promoter region contained several segments which appeared to enhance the activity of the minimal promoter. One such enhancer sequence was homologous to an enhancer previously described in the human elastase promoter. Activity of the 594-bp MPO promoter in HL-60 was reduced by only approximately 30% following treatment of the cells with chemical inducers of maturation, but the 1099-bp MPO promoter showed 60% reduction in activity after DMSO treatment. A previously described enhancer region in intron 9 of the MPO gene had little or no effect on activity of the 594-bp MPO promoter. The availability of the MPO promoter will facilitate determination of other factors involved in the regulation of this myeloid-specific gene.
Leukemia 1995 May
PMID:Identification and characterization of the human myeloperoxidase promoter. 776 48

Induced differentiation of the promyelocytic leukaemia cell line, HL-60, is associated with the acquisition of functional properties, like the expression of specific receptors and the competence to exert the respiratory burst (RB). In this system we evaluated the effects of ionizing radiation on the signal transduction processes involved in the activation of the respiratory burst/NADPH oxidase. HL-60 cells were X-irradiated with up to 1 Gy and induced towards granulocytic differentiation by treatment with 1.25% DMSO on day 0. The expression of the formyl peptide receptor (FPR), the development of responsiveness of the cells to its ligand (f-MLP) and to 4 beta-phorbol 12-myristate 13-acetate (PMA) were measured up to day 7 postinduction/irradiation. Using flow cytometry, fluorescinated formyl-hexapeptide or unlabelled f-MLP as ligands and dihydrorhodamine 123 (DHR 123) as an indicator of RB activity, respectively, the acquisition of functional responsiveness to both stimuli was determined. Immature FPR were identified at day 2 after induction which responded to the agonist from day 3 on. F-MLP receptor-mediated RB oxidase activation was completely radioresistant to 1 Gy, while protein kinase C (PKC)-stimulated triggering of the enzyme via PMA was inhibited by about 50% by 0.5 and 1.0 Gy. We conclude that different signal transduction pathways as triggered by f-MLP and PMA respectively exhibit differences in radiosensitivity, with PKC subspecies and downstream responses being possible sites of radiation damage.
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PMID:Differences in radiosensitivity of the respiratory burst generated in HL-60 cells via different signal transduction pathways. 781 75

The p53 tumor suppressor gene plays a role in controlling a G1 phase checkpoint. The WAF1/CIP1 gene with encodes p21WAF1/CIP1 protein, an inhibitor of cyclin-dependent kinases, is a downstream mediator of p53 function. We examined expression of the WAF1/CIP1 gene and its relationship to growth arrest and differentiation in p53-null human leukemic cell lines. We show that p53-independent induction of WAF1/CIP1 occurs in human leukemia cells treated with 12-O-tetradecanoylphorbol-13-acetate, okadaic acid, or IFN-gamma but not with retinoic acid, vitamin D3, or DMSO. Furthermore, WAF1/CIP1 induction correlates with growth arrest associated with monocyte-macrophage differentiation. The present studies support the idea that WAF1/CIP1 gene expression can be regulated through multiple mechanisms, suggesting that strategies may be designed to restore the G1 checkpoint controls in p53-null cells by targeting these p53-independent mechanisms of WAF1/CIP1 induction.
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PMID:p53-independent induction of WAF1/CIP1 in human leukemia cells is correlated with growth arrest accompanying monocyte/macrophage differentiation. 783 38


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