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)

Our recent establishment of several permanent in-vitro cell lines from Brown Norway rat leukemia (BNML) and the development of a clonogenic assay prompted us to undertake detailed studies on the growth control mechanism of a cell type which for several years has served as an animal model for human AML and preclinical studies. So far, these cells have no defined biological regulators but require intricate cellular interactions to sustain their growth. The effects on cell growth and clonogenicity, of agents known to modify the intracellular levels of cyclic nucleotides, were analysed. Here we report that CT binding strongly inhibited cell growth at a wide range of concentrations (10(-6)-10(-14) M) while beta chain pentameric subunits or alpha chain had no effects. Cell growth was inhibited in a dose-dependent manner. The ligand-receptor interactions mediated the alpha chain's transit through the membrane; the adenylate cyclase activation and the rise in c-AMP levels (60 min) resulted in DNA synthesis arrest (5 h), then finally ended in cell death (24-48 h). A significant decrease in the clonal ability of treated cultures was seen. A decrease of up to five logs in the clonogenic cell number was observed after 48 h of toxin treatment (10(-7) M). The growth inhibition of CT were reproduced by several agents (PGE, theophylline, isobutylmethylxanthine) known to raise intracellular c-AMP levels. Data are commented from a biochemical approach to intracellular events controlling the cell growth of this leukemia. The potential interests of c-AMP inducing agents on the eradication of this leukemia by ex-vivo marrow treatments are also considered.
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PMID:On growth regulation of the rat promyelocytic leukemia (BNML): growth inhibition and eradication of clonogenic cells by cholera toxin. 243 59

The human T-cell leukemia virus type I (HTLV-I) trans-activator (tax)-inducible enhancer was localized to three copies of 21-base-pair repeats within the long terminal repeat. Interestingly, the TGACG motif found in the center of the 21-base-pair tax-responsive element (TRE) is also present in the cyclic AMP (cAMP)-responsive elements (CREs) and activating transcription factor (ATF)-binding sites. In this study, we demonstrate that the three TRE-binding proteins, TREB-1, TREB-2, and TREB-3, also bind to various CREs and ATF-binding sites and that the TREs can confer upon a heterologous promoter responsiveness to various inducing agents, including tax, cAMP, and E1a. Furthermore, the transcriptional activation of the HTLV-I promoter by tax can be inhibited by several protein kinase inhibitors, including sangivamycin. Our results indicate that the TREs, CREs, and ATF-binding sites are similar cis-acting elements and further suggest (i) that the transcriptional activation of the HTLV-I promoter by tax involves the action of a protein kinase and (ii) that induction by tax, cAMP, and E1a might be mediated by distinct factors or kinases.
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PMID:Utilization of signal transduction pathway by the human T-cell leukemia virus type I transcriptional activator tax. 247 73

The sequences that control transcriptional initiation of the provirus of the human T-cell leukemia virus type 1 (HTLV-1) are shown to be responsive to intracellular levels of cyclic AMP. A heptanucleotide sequence present within the 21-nucleotide repeat sequence that is similar to the cyclic AMP-responsive consensus (CRE) sequence was required for cyclic AMP-mediated increase in gene expression. Although the CRE-like sequences were contained within sequences that were responsive to the virally encoded trans-activator (tax), the evidence presented indicates that the mechanisms of promoter induction by the tax product and cyclic AMP are independent. The implication of cyclic AMP stimulation of HTLV-1 provirus gene expression for long-term persistence of infected T cells and for virus-induced transformation is discussed.
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PMID:Response of the human T-cell leukemia virus type 1 long terminal repeat to cyclic AMP. 253 45

The trans activator (p40tax) of human T-cell leukemia virus type I (HTLV-I) is a transcriptional factor that activates the long terminal repeat (LTR) of HTLV-I and interleukin-2 receptor alpha. We examined the HTLV-I enhancer responsible for tax-mediated trans activation and identified (A/T)(G/C)(G/C)CNNTGACG(T/A) as a plausible tax-responsive element (TRE). The putative TRE in the LTR was found to be different from the elements required for activation by cycle AMP and 12-O-tetradecanoylphorbol-13-acetate, although these elements overlapped each other. The TRE was also different from a binding site of an NF-kappa B-like factor that was identified in the interleukin-2 receptor alpha promoter and human immunodeficiency virus LTR as a TRE. The latter result was further demonstrated by the failure of the NF-kappa B sequence to compete with the TRE of the LTR in a protein-binding assay. These findings indicate that tax function and its cascade can modulate activities of various enhancer sequences, which are probably regulated by distinct DNA-binding factors.
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PMID:A unique enhancer element for the trans activator (p40tax) of human T-cell leukemia virus type I that is distinct from cyclic AMP- and 12-O-tetradecanoylphorbol-13-acetate-responsive elements. 254 1

A transcriptional trans-acting factor p40tax of human T-cell leukemia virus type I (HTLV-I) functions as an inducer for expression of HTLV-I provirus via activation of the enhancer in the long terminal repeat of HTLV-I. In addition to p40tax and a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, we report here that forskolin, an activator of adenyl cyclase, also induces function of the HTLV-I enhancer. Experiments with mutants of the HTLV-I enhancer revealed that TPA-induced activation was not mediated by solely a 21-base-pair (bp) sequence that is repeated three times in the enhancer, whereas the 21-bp enhancer element can act as a sufficient cis-acting sequence for activation by both p40tax and forskolin. In addition, we found that nuclear factor(s) like the cyclic AMP-responsive element (CRE) binding factor could bind to the HTLV-I 21-bp enhancer element. However, a difference was found in sequences required for activation by p40tax and forskolin. A CRE related sequence present in the 21-bp enhancer element was enough for forskolin-induced activation. On the other hand, p40tax required a much longer sequence that is overlapping but not identical to the CRE related sequence, suggesting that the forskolin-induced cyclic AMP pathway may be partly involved in, but not sufficient for p40tax-mediating trans-activation of the HTLV-I enhancer.
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PMID:Differential activation of the 21-base-pair enhancer element of human T-cell leukemia virus type I by its own trans-activator and cyclic AMP. 254 56

The effects of the differentiation-inducing agents N6, O2'-dibutyryl cyclic AMP, beta-all-trans retinoic acid, dimethylsulfoxide and butyrate on the levels of galactoside-binding proteins (lectins) in cultured human and murine tumor cells were examined by immunoblotting. Differentiation was associated with decreased levels of a 34-kDa lectin in the K-1735P and B16-F1 melanoma cells and decreased levels of a 14.5-kDa lectin in S20 neuroblastoma, MDA-MB 175 breast carcinoma, HL-60 and THP-1 leukemia cells. The level of a 14.5-kDa lectin increased during differentiation of F-9 embryonal and KM12P colon carcinoma cells. These results indicate that tumor cell differentiation along specific pathways is accompanied by distinct modulation of lectin expression. These changes may recapitulate the normal developmental regulation of lectin expression.
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PMID:Modulation of galactoside-binding lectins in tumor cells by differentiation-inducing agents. 255 43

Heat-inactivated rabbit antiserum, in the absence of complement, induced a 1.5-2-fold increase in cyclic AMP levels in target cells L5178Y leukemia lymphoblasts within 10-20 min after the experiment. This change preceded the previously reported delayed inhibitory effects of antiserum on cell growth such as inhibition of RNA, DNA, and protein synthesis and cell proliferation, suggesting that cyclic AMP may be one of the mediators of the antigen-antibody reactions which occur at the cell surface. Furthermore, the addition of cyclic GMP or excess calcium to either antiserum or cyclic AMP-treated cultures alleviated the growth inhibitory effects of either antiserum or cyclic AMP, substantiating further the hypothesis proposed.
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PMID:Role of cyclic AMP in antiserum-induced growth inhibition of murine leukemia L5178Y cells. 258 12

Between January 1980 and March 1983, a study was conducted on the effects of intensification therapy in 20 adult acute leukemia patients who had achieved complete remission with induction therapy. Intensification therapy consisted of cyclic administration of six combination therapies given at gradually longer intervals, using daunorubicin, cytosine arabinoside, 6-mercaptopurine and prednisolone (DCMP), cyclocytidine (DCyMP), vincristine (DCVP), behenoyl-ara-c (BHAC-DMP), aclacinomycin (BHAC-AMP) and (ACM-MP). Six combinations were given sequentially at one-month intervals, at 2-, 3-, 4-, 5- and eventually 6-month intervals, until 5-year survival. The median remission duration was 38 months for AML, and 17 months for ALL. The median survival was 66 months for AML, and 37 months for ALL. The five year survival rate was 50%. Nine of the 20 patients are still alive. Methotrexate and prednisolone were administered intrathecally for prophylaxis of CNS leukemia on Day 4 for each intensification therapy. There was no CNS leukemia. This intensification protocol was shown to be effective in improving the prognosis of adults acute leukemia.
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PMID:[An intensification therapy of adults acute leukemia]. 264 96

In the present study, we examined the effect of prostaglandin E1 (PGE1) on Ca2+ mobilization in a human megakaryocyte (the progenitor of platelets) leukemia cell line, designated as CMK. PGE1 caused a rapid and dose-dependent increase in the intracellular free calcium level ([Ca2+]i) associated with the elevation of cyclic AMP. The PGE1-induced elevation of [Ca2+]i was decreased by the prior addition of ethylene glycol bis(2-aminoethylether)tetraacetic acid to the medium by approximately 25% of the control. This result indicates that the PGE1-induced elevation of [Ca2+]i is due to influx of Ca2+ from the external medium and to mobilization of Ca2+ from intracellular stores. Pretreatment of CMK cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), a stimulus for protein kinase C, further enhanced the PGE1-induced increase in the cellular cyclic AMP level. Inversely, pretreatment of CMK cells with TPA (10 nM), prior to the addition of PGE1, inhibited the PGE1-induced elevation of [Ca2+]i. Dibutyryl cyclic AMP and forskolin did not elevate [Ca2+]i or affect the PGE1-induced Ca2+ mobilization. The inhibitory action of TPA in the PGE1-induced elevation of [Ca2+]i was mimicked by other protein kinase C-activating agents, such as 1-oleoyl-2-acetylglycerol and N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide, and was selectively restored by protein kinase C inhibitors, such as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride. Thus, the inhibitory modulation of TPA on the PGE1-induced elevation of [Ca2+]i is mediated through protein kinase C activation. PGE1 had no inductional effect of megakaryocytic phenotypic changes in CMK cells. The biological role of PGE1, which increased [Ca2+]i and cyclic AMP levels in the CMK cells, remains to be determined.
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PMID:Elevation of intracellular calcium ion by prostaglandin E1 and its inhibition by protein kinase C in a human megakaryocyte leukemia cell line. 273 22

38 consecutive, previously untreated adult patients with acute non-lymphocytic leukaemia (ANLL) were treated with BHAC-AMP (N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine, aclacinomycin A, 6-mercaptopurine, and prednisolone) therapy between March 1980 and February 1985. 25 patients (65.8%) achieved complete remission (CR). Median CR duration and median survival of patients who achieved CR were 14, and 24 months, respectively. The Kaplan-Meier analysis revealed a probability for remaining in CR of 18.0% at 5 years. Analysis of failure cases revealed that most of them were due to resistant disease. Major toxicities were infection, diarrhoea, liver dysfunction, nausea and vomiting but these were acceptable. The results indicate that BHAC-AMP therapy is comparable to the regimen with daunorubicin and cytosine arabinoside and a further clinical trial is necessary for previously untreated adult patients with ANNL.
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PMID:Behenoyl cytosine arabinoside, aclacinomycin A, 6-mercaptopurine, and prednisolone combination therapy for acute non-lymphocytic leukaemia in adults. 276 38


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