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)

In this study, we have examined the synthesis of heat shock protein (HSP70) in leukemia cells from acute myelogenous leukemia (AML) patients and in mononuclear cells from normal individuals, before and after growth factor stimulation. We have shown that the HSP70 protein was expressed in these cells in the absence of temperature elevation. Stimulation of proliferation of AML cells by the growth factors interleukin-3 and granulocyte-macrophage colony-stimulating factor and stimulation of normal lymphocytes by phytohemagglutinin (PHA) resulted in decreased synthesis of HSP70, suggesting that high levels of HSP70 are associated with cellular differentiation.
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PMID:Proliferation of hematopoietic cells is accompanied by suppressed expression of heat shock protein 70. 155 May 80

Cyclopentenone prostaglandins PGA1 and PGJ2 can inhibit the growth of HTLV-1 infected cord blood-derived human mononuclear cells (CBMC), both after acute infection and in chronically infected, immortalized cells. When CBMC were exposed to HTLV-1 infection by coculturing with lethally irradiated, virus-donor allogeneic MT-2 cells, they underwent a proliferative response, that peaked within the first week and then declined. PG treatment did not inhibit the initial proliferation (day 4) of cocultured CBMC, while multiple treatments with PGA1 and more efficiently with PGJ2, suppressed the late cell proliferation (from day 8 onward). The pharmacological effects of PGA1 and PGJ2 were reversible and therefore multiple treatments were required to maintain their antiproliferative activity. Increasing concentrations (20, 40, 80 IU/ml) of recombinant IL-2 did not affect the virus-associated proliferative response of CBMC, and exogenous IL-2 did not revert the antiproliferative effect of both PGs. Arrest of proliferation in cocultured CBMC occurred concomitantly with expression of high levels of HSP70 in the cells. In fact, though HSP70 expression was induced early (day 5) after exposure to HTLV-1, its expression was further increased after multiple PG treatments and high levels were found when the antiproliferative effect of PGs became manifest. Since HSP70 protein family is involved in the control of cell cycle as well as in antigen processing and presentation during the immune response against tumor cells and pathogens, the persistent expression of this protein in PG-treated cocultures suggested that, beside inhibiting the growth of virus-infected cells, HSP70 expression might play a role in modulating the immune function of CBMC. However, unlike in most virus infection models, in which cyclopentenone PGs exert clear antiviral effects by inhibiting the synthesis and maturation of virus proteins, no antiviral activity was found in this model of infection. This strongly suggests that the main effect of these PGs against HTLV-1 infected cells consists in inhibiting proliferation in vitro without affecting viral expression.
Leukemia 1994 Jun
PMID:Antiproliferative activity of cyclopentenone prostaglandins in early HTLV-1 infection is independent of IL-2 and is associated with HSP70 induction. 751 27

A novel human gene, ARCN1, has been identified in chromosome band 11q23.3. It maps approximately 50 kb telomeric to MLL, a gene that is disrupted in a number of leukemia-associated translocation chromosomes. cDNA clones representing ARCN1 hybridize to 4-kb mRNA species present in all tissues tested. Sequencing of cDNAs suggests that at least two forms of mRNA with alternative 5' ends are present within the cell. The mRNA with the longest open reading frame gives rise to a protein of 57 kDa. Although the sequence reported is novel, remarkable similarity is observed with two predicted protein sequences from partial DNA sequences generated by rice (Oryza sativa) and fruit fly (Drosophila melanogaster) genome projects. The degree of sequence conservation is comparable to that observed for highly conserved structural proteins, such as heat shock protein HSP70, and is greater than that of gamma-tubulin and heat shock protein HSP60. A more distant relationship to the group of clathrin-associated proteins suggests a possible role in vesicle structure or trafficking. In view of its ancient pedigree and a potential involvement in cellular architecture, we propose that the ARCN1 protein be named archain.
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PMID:The human archain gene, ARCN1, has highly conserved homologs in rice and Drosophila. 778 67

In mice, homozygosity for the Mhc haplotype H-2k is associated with increased susceptibility to spontaneous and virus-induced leukemia, lymphoma and other neoplasms in the predisposed host. The influence of the Mhc on malignant development in these models is to shorten the latency after virus inoculation. Here, we present evidence that a similar phenomenon results in early-onset of human leukemia. A molecular analysis of the MHC in 112 CML patients showed that those who developed the disease when aged less than 35 years (early-onset group) had higher homozygosity rates for the DOA1, HSP70 and C4 alleles of the DR53 group of ancestral haplotypes, for a subtype of HLA-A3, and a higher allele frequency of BfFb compared to the late-onset group. The oldest patient (n = 13) homozygous for DR53 was 52-years-old (p = 0.004), and all HLA-A3 homozygous patients (n = 4) were in the early-onset group (p = 0.01). The relative risk for early-onset CML yielded by HLA-A3 homozygosity was 17.6. The well-known serological HLA-Cw4 association was not confirmed at the DNA level and thought to be due to linkage disequilibrium with BfFb. The factor B association was sex-limited. The DR52 group haplotypes appeared to be protective. The HLA-identical sibling frequency was increased only in the early-onset group (p < 0.01). Our findings agree with the concept of an MHC influence on the development of malignancies. The similarity in the location of the susceptibility loci and the serological cross-reaction between H-2Ek and DR53 raise the possibility that the mouse and human MHC share the same leukemia susceptibility genes.
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PMID:Human major histocompatibility complex contains several leukemia susceptibility genes. 790 66

Differentiation of cells of myelomonocitic lineage influences both cellular permissivity to infection with human T-cell leukemia virus type I after cell-to-cell virus transmission and sensitivity to the antiproliferative effect of cyclopentenone prostaglandins (PG)A1 and PGJ2. Growth inhibition and control of infection were found to be associated with high intracellular levels of inducible p72 heat shock protein (HSP70). Pluripotent K562 cells produced higher HSP70 base-line levels than promyelocytic HL60 or monoblastoid U937 cells. Treatment with PGA1 and especially with PGJ2 enhanced the synthesis of HSP70 in all these cells. Notably, HSP70 accumulated in virus-exposed U937 cells (but not in K562 or HL60 cells). Because in lethally irradiated virus-donor cells HSP70 production was barely detectable, expression of this protein in cocultured U937 cells can be prevalently attributed to virus-recipient cells. Treatment with PGA1 and even more with PGJ2 remarkably enhanced the synthesis of HSP70 in virus-exposed U937 cells, thus resulting in persistently high levels of HSP70 protein in the cells. As shown previously, in U937 cells treatment with PGs was associated with reduced percentages of virus p19gag positive cells and enhanced specific lysis of virus-donor cells at early time points after cell-to-cell transmission. Because the HSP70 protein family is involved in the control of cell proliferation as well as in antigen processing function during the immune response to pathogens, it is possible that persistent high expression levels of HSP70 in PG-treated cells play a critical role in regulating both cell cycling and antiviral cellular responses.
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PMID:Effects of cyclopentenone prostaglandins on myeloid cells during early infection with HTLV-I. II. Regulation of synthesis of inducible p72 heat shock protein. 796 71

Cyclopentenone prostaglandins (PGs) induce the synthesis of heat shock proteins (HSPs) in mammalian cells. Since arachidonic acid metabolites are implicated in the control of fever, we investigated the effect of PG treatment on thermal injury in human K562 erythro-leukemia cells. Prostaglandin A1 (PGA1) was found to protect cells after severe heat shock and to induce a thermotolerant state, which persisted for 24-48 h. Prostaglandins of the B, E, and F type were not effective. Kinetics of thermotolerance induction was comparable to heat-induced heat resistance. Establishment of a thermotolerant state was not a direct effect of PGA1, since it was dependent on de novo protein synthesis and was associated with HSP70 induction. This activity of PGA1 could be part of a protective control mechanism during fever.
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PMID:Induction of thermotolerance by prostaglandin A in human cells. 834 76

Interferon (IFN) alpha and beta can activate an antiviral and immunomodulating response in primary cord blood-derived mononuclear cells (CBMC) exposed to infection with Human T-cell Leukemia Virus type I (HTLV-I), resulting in partial inhibition of early infection in vitro. On the other hand, PGA1, a PGE1-derived cyclopentenone prostaglandin, can inhibit in vitro the proliferation of virus-infected CBMC, preventing the emergence of the potentially transformed clone. In order to achieve a complete control of HTLV-I infection in this experimental model, we evaluated whether the antiviral activity of IFNs and the antiproliferative activity of PGA1 could be preserved in a combination therapy scheme. Recipient CBMC were treated with IFN alpha or beta (1000 IU/ml) at the onset of the co-culture with lethally irradiated virus-donor MT-2 cells, followed by multiple treatments with PGA1 (4 micrograms/ml every 4 days, starting on day 0) for 6 weeks post infection (p.i.). In PGA1-treated co-cultures the percentage of virus-positive CBMC was constantly doubled during culture time as well as the amount of viral transcripts and p19 virus core protein production were increased. The antiviral effects of IFNs, resulting in about a 50% reduction of the percentage of virus-positive CBMC and consequently in a partial inhibition of virus expression (HTLV-I transcription and p19 production) until 4 weeks p.i., were suppressed by multiple PGA1 treatments. However, the antiproliferative effect of PGA1 was enforced in IFN-treated co-cultures, leading to earlier control of proliferation of virus-infected cells. Interestingly, infection of CBMC with HTLV-I was associated with persistent expression of 70 kDa heat shock protein (HSP70), for at least 4 weeks p.i. IFNs and PGA1 showed antagonistic effects on HSP70 production in infected CBMC. In fact, production of HSP70 was suppressed (or prevented) in IFN-treated co-cultures, tested 2 and 4 weeks p.i. The fact that the expression of HSP70 is apparently suppressed (or prevented) by IFN treatment is surprising, since expression of this protein family has been associated with antiviral immunity. PGA1 could totally reverse the IFN-mediated suppression of HSP70 expression in these co-cultures. It is presently unclear whether HSP70 expression is directly involved in the control of proliferation exerted by PGA1 against virus-infected CBMC or is an epiphenomenon associated with inhibition of cell growth.
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PMID:Combined treatments with interferon (alpha,beta) plus PGA1 to control early infection with HTLV-I in primary cord blood-derived mononuclear cells. 846 16

The Fas/Apo-1 molecule is a member of tumor necrosis factor/nerve growth factor (TNF/NGF) receptor family and is able to induce apoptosis in various type of malignant cells, including most of the human leukemia T-cells. We previously demonstrated that the Fas-resistant variants may exist in highly Fas-sensitive human leukemia T-cell lines. The surface expression of Fas antigen was unchanged in the variant cells, suggesting the requirement of the cytoplasmic mechanism to exert apoptosis. In the present study, we examined the changes in cytoplasmic proteins of the Fas-sensitive and Fas-resistant cells after stimulation with anti-Fas antibody, 2D1. In Western blotting analysis, we found that the stimulation of Fas-sensitive cells with 2D1, but not resistant variants, induced a repression of cyclin-dependent kinases (cdks), p34cdc2 and p33cdk2, along with apoptosis. There was no alteration in the expression of bcl-2, HSP70, HSP90, and cyclin proteins examined. This observation seemed specific to Fas-mediated apoptosis, because calcium ionophore A23187 or sodium azide failed to repress the expression of cdks. These results indicate that the specific depletion of cdks, most likely due to proteolysis, may play a role in Fas-mediated apoptosis.
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PMID:Selective depletion of cyclin-dependent kinases is associated with Fas-mediated apoptosis in human leukemia T-cell lines. 878 21

The expression of three heat shock proteins (HSPs)-HSP90 alpha, HSP70, HSP27 in cells obtained from 22 patients with leukemia, K562 erythroleukemia cell line, and normal blood cells was observed by means of RNA dot blot analysis. The results showed that the expression of the HSP27 gene was enhanced in 4 cases of acute lymphoid leukemia (ALL), 7 cases of acute nonlymphoid leukemia (ANLL) and 2 cases of myelodysplastic syndrome (MDS) as compared with that of the normal blood cells, yet there was no significant difference in the HSP27 expression between the ALL and ANLL cells. The expression of HSP70 in all the 5 ALL and ANLL patients was much lower than that of the normal subjects, except 1 case of ALL and 1 case of MDS, in which the expression was obviously enhanced. All the cases including 11 ANLL, 5 ALL and 1 MDS had higher HSP90 alpha expression than the normal subjects. The enhanced expression of HSP90 alpha in leukemia cells may be associated with the active and indefinite proliferation of leukemia cells. Our results also suggest that the high expression of the HSP27 gene may not be confined to a specific type of acute leukemia.
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PMID:Study of heat shock protein HSP90 alpha, HSP70, HSP27 mRNA expression in human acute leukemia cells. 938 84

Cytosol and nuclei of Lewis lung carcinoma (LLC) cells contain high affinity binding sites specific for the arachidonic acid metabolite 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE). In this report we present evidence that the cytosolic 12(S)-HETE binding complex also occurs in human erythroleukemia (HEL) and promonocytic leukemia (U937) cells as well as in murine 3T3-L1 preadipocytes but not in intestinal epithelial cells (Int407). The cytosolic 650 kDa 12(S)-HETE-binding complex was found to consist of subunits; raising the ATP concentration in cytosol led to conversion of the 650 kDa complex to a 50 kDa binding component, presumably the actual 12(S)-HETE binding polypeptide. Lowering of the cytosolic concentration of ATP had the opposite effect, i.e., the amount of the 650 kDa complex increased. Another subunit of the 650 kDa complex was identified as heat shock protein 70 (hsp70) by Western blot analyses and coimmunoprecipitation. Hsp70 was present in substoichiometric amounts, in an approximate 1:6 ratio. The multimeric nature of the binding complex and the identification of hsp70 as a subunit suggest that there are similarities between the 12(S)-HETE binding protein and receptors of the steroid/thyroid hormone superfamily.
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PMID:Identification of subunits of the 650 kDa 12(S)-HETE binding complex in carcinoma cells. 950 84


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