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)

Platelets of patients with thrombocytosis following splenectomy, in chronic granulocytic leukaemia and in polycythaemia vera were separated into five fractions by centrifugation in discontinuous Ficoll density gradient. Platelet volume, content of protein and enzyme activities of lactic dehydrogenase, phosphoglycerate kinase and glyceraldehyde phosphate dehydrogenase were distinctly higher for the three groups in the heavy fraction IV compared with the light fraction I. With regard to the platelet volume, however, these differences were compensated almost completely like in the normal persons.
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PMID:[Enzyme activities in platelets of different specific gravity in thrombocytosis of various etiology (author's transl)]. 27 77

Housekeeping genes, particularly actin, tubulin, and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are widely used to estimate the amount and integrity of RNA in Northern blotting. In this work, the most reliable housekeeping gene for gene expression analysis of Hodgkin's disease (HD) lymph nodes was determined by comparing the conventional housekeeping genes, beta-actin, beta-tubulin, GAPDH, and the mouse gene LLRep3, that had been used previously in gene expression studies. It was found that the amounts of mRNA in these genes are very heterogeneous in HD lymph nodes. In contrast, their expression was relatively constant in tonsils undergoing a chronic inflammatory process. It is concluded that none of the housekeeping genes tested is suitable for the fine quantitative analysis of gene expression in HD lymph nodes.
Leukemia 1991 Dec
PMID:Expression of housekeeping genes in Hodgkin's disease lymph nodes. 177 60

Methylglyoxal induced growth arrest in the G1 phase of the cell cycle and toxicity in human leukaemia 60 cells in vitro. Inhibition of DNA synthesis but not inhibition of RNA synthesis, protein synthesis or inhibition of glyceraldehyde-3-phosphate dehydrogenase activity correlated with cytotoxicity. Incubation of human leukaemia 60 cells with methylglyoxal led to the rapid accumulation of adducts of methylglyoxal with DNA, and a lower accumulation of methylglyoxal adducts with RNA and protein in the initial hour of culture; fragmentation of nuclear DNA characteristic of apoptosis developed in the second hour of culture. Methylglyoxal induced apoptosis in human leukaemia 60 cells but did not affect the growth and viability of concanavalin A-stimulated human peripheral lymphocytes in vitro. These effects confirm and further substantiate the anti-proliferative anti-tumour activity of methylglyoxal in vitro, which may mediate the anti-tumour activity of glyoxalase I inhibitors in vivo.
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PMID:Effect of methylglyoxal on human leukaemia 60 cell growth: modification of DNA G1 growth arrest and induction of apoptosis. 868 79

Heme and a series of synthetic heme analogs were tested for inhibition of human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT) activity. Heme and the protoporphyrin complexes of cadmium, magnesium, and tin significantly inhibited HIV-1 RT, whereas other metalloporphyrins had a lesser or no effect on the enzyme. The mechanism of inhibition was examined with respect to heme and tin protoporphyrin (SnPP), as both compounds have been utilized clinically as treatment for noninfectious disorders. Heme and SnPP inhibited HIV-1 RT in a noncompetitive manner with respect to deoxythymidine triphosphate. Inhibition depended in part on the protoporphyrin structure, because the mesoderivatives of the heme analogs essentially were without effect. Heme also markedly enhanced the inhibitory effect of azidothymidine (zidovudine, AZT) on HIV-1 RT, and the combination of the two compounds showed synergy in inhibiting HIV-1 RT. HIV-1 RT was used to reverse transcribe the glyceraldehyde phosphate dehydrogenase (GAPDH) gene from human kidney. Subsequently, GAPDH cDNA was amplified with Taq polymerase, and electrophoresis showed that HIV-1 RT catalyzed the reverse transcription of human mRNA at a rate comparable to that of Moloney murine leukemia virus. Heme and SnPP prevented cDNA synthesis by HIV-1 RT in this RT-polymerase chain reaction assay. We also examined the effects of these compounds on normal human bone marrow function. Heme stimulated both erythroid and myeloid progenitor colony formation, whereas SnPP was essentially without effect. In contrast, ZnPP had a suppressive effect on hematopoiesis. Finally, we show that heme has a sparing effect against the myelotoxicity of AZT. The results of these studies raise the possibility that combination therapy with AZT and heme, or heme plus an inhibitor of heme catabolism, might have therapeutic potential in the acquired immunodeficiency syndrome.
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PMID:Inhibition of human immunodeficiency virus-1 reverse transcriptase by heme and synthetic heme analogs. 883 64

The promyelocytic leukaemia (protein) (PML) localizes to multiprotein complexes known as PML nuclear bodies. We found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) co-immunoprecipitates with PML and co-localizes with PML in nuclear bodies. RNase treatment disrupts the ability of PML and GAPDH to both co-localize and co-immunoprecipitate, indicating that the association between PML and GAPDH depends on the presence of RNA. Disruption of PML bodies contributes towards reduced apoptosis in acute promyelocytic leukaemia and GAPDH induces apoptotic neuronal death. The GAPDH-PML interaction may be involved in the regulation of apoptosis.
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PMID:Demonstration of a RNA-dependent nuclear interaction between the promyelocytic leukaemia protein and glyceraldehyde-3-phosphate dehydrogenase. 979 12

Apoptosis was induced by treating L1210 leukaemia cells with mechlorethamine, and SW620 colorectal cells with doxorubicin. The onset and progression of apoptosis were monitored by assessing caspase activation, mitochondrial transmembrane potential, phosphatidylserine externalization, DNA fragmentation and cell morphology. In parallel, 31P magnetic resonance (MR) spectra of cell extracts were recorded. In L1210 cells, caspase activation was detected at 4 h. By 3 h, the MR spectra showed a steady decrease in NTP and NAD, and a significant build-up of fructose 1,6-bisphosphate (F-1,6-P) dihydroxyacetonephosphate and glycerol-3-phosphate, indicating modulation of glycolysis. Treatment with iodoacetate also induced a build-up of F-1,6-P, while preincubation with two poly(ADP-ribose) polymerase inhibitors, 3-aminobenzamide and nicotinamide, prevented the drop in NAD and the build-up of glycolytic intermediates. This suggested that our results were due to inhibition of glyceraldehyde-3-phosphate dehydrogenase, possibly as a consequence of NAD depletion following poly(ADP-ribose) polymerase activation. Doxorubicin treatment of the adherent SW620 cells caused cells committed to apoptosis to detach. F-1,6-P was observed in detached cells, but not in treated cells that remained attached. This indicated that our observations were not cell line- or treatment-specific, but were correlated with the appearance of apoptotic cells following drug treatment. The 31P MR spectrum of tumours responding to chemotherapy could be modulated by similar effects.
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PMID:Magnetic resonance detects metabolic changes associated with chemotherapy-induced apoptosis. 1036 12

We evaluated the usefulness of a recently developed real-time reverse transcriptase polymerase chain reaction (RT-PCR) system to detect minimal residual diseases (MRD) in patients with acute myelogenous leukaemia (AML) with chromosomal translocation t(8:21). The method was simple, rapid and reproducible for the quantity of chimeric AML1-ETO (MTG8) transcripts. The ratio of the absolute copy number of a target gene (AML1-ETO) to a control gene (glyceraldehyde-3-phosphate dehydrogenase, GAPDH) was calculated by using a fluorescence curve prepared from amplicons of serially diluted standard RNA. The relative points of MRD in bone marrow (BM) of 8 patients in the acute phase of the disease was from 0.85 to 3.0, whereas those of MRD in complete remission (CR) decreased to below 6.4 x 10(-3). This method was also applied to evaluate chimeric transcripts in peripheral blood (PB) samples. The values in patients with t(8;21) AML were from 0.97 to 2.0 in the acute phase, whereas those in CR showed less than 2.2 x 10(-4). There was 10(-5)-fold difference in AML1-ETO mRNA expression between PB samples in the acute phase and those in CR. The results suggest that we may easily monitor MRD in patients with t(8;21) AML through quantitative analysis of AML1-ETO transcripts in blood samples.
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PMID:A quantitative reverse transcriptase polymerase chain reaction method for the detection of leukaemic cells with t(8;21) in peripheral blood. 1077 97

Overexpression of SSAT (polyamine catabolic enzyme) in female mice results in impaired ovarian folliculogenesis and uterine hypoplasia. To identify the molecular basis for this, the gene expression profiles in uterus and ovary and for comparison, liver and kidney, from non-transgenic (NT) and SSAT transgenic (ST) mice were compared. The mRNA abundance for lipoprotein lipase and glyceraldehyde-3-phosphate dehydrogenase was elevated in all four ST (>NT) tissues. The translation initiation factor-3 subunit 5 mRNA, and transcripts related to endogenous murine leukemia provirus (MLV-related) and murine retrovirus-related sequences (MuRRS) were decreased in ST tissues. A novel calmodulin-related mRNA was strongly induced in ST liver and kidney. SSAT overexpression was associated with increased levels of IGF-binding protein-2 (IGFBP-2) in the uterus and ovary, and a reduction in IGFBP-3 mRNA levels in the uterus. Exogenous spermidine and spermine elevated endogenous IGFBP-2 and SSAT mRNA abundance, whereas, putrescine stimulated IGFBP-2 mRNA abundance and transfected IGFBP-2 gene promoter activity in human (Hec-1-A) uterine cells. Sp1 and BTEB1 mRNAs that encode transcription factors for the IGFBP-2 gene also were induced in some ST tissues. The data suggest that SSAT and polyamines are important for the control of molecular pathways underlying reproductive tract tissue growth, phenotype, and function.
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PMID:Altered levels of growth-related and novel gene transcripts in reproductive and other tissues of female mice overexpressing spermidine/spermine N1-acetyltransferase (SSAT). 1170 47

Thiopurine treatment of human leukemia cells deficient in components of the mismatch repair system (Nalm6) initiated apoptosis after incorporation into DNA, as revealed by caspase activation and terminal deoxynucleotidyl transferase-mediated nick end labeling assay. To elucidate the cellular sensor(s) responsible for recognition of DNA damage in cells with an inactive mismatch repair system, we isolated a multiprotein nuclear complex that preferentially binds DNA with thioguanine incorporated. The components of this nuclear multiprotein complex, as identified by protein mass spectroscopy, included high mobility group proteins 1 and 2 (HMGB1, HMGB2), heat shock protein HSC70, protein disulfide isomerase ERp60, and glyceraldehyde 3-phosphate dehydrogenase. The same complex was also shown to bind synthetic oligodeoxyribonucleotide duplexes containing the nonnatural nucleosides 1-beta-D-arabinofuranosylcytosine or 5-fluoro-2'-deoxyuridine. Fibroblast cell line derived from Hmgb1(-/-) murine embryos had decreased sensitivity to thiopurines, with an IC(50) 10-fold greater than Hmgb1-proficient cells (P < 0.0001) and exhibited comparable sensitivity to vincristine, a cytotoxic drug that is not incorporated into DNA. These findings indicate that the HMGB1-HMGB2-HSC70-ERp60-glyceraldehyde 3-phosphate dehydrogenase complex detects changes in DNA structure caused by incorporation of nonnatural nucleosides and is a determinant of cell sensitivity to such DNA modifying chemotherapy.
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PMID:A nuclear protein complex containing high mobility group proteins B1 and B2, heat shock cognate protein 70, ERp60, and glyceraldehyde-3-phosphate dehydrogenase is involved in the cytotoxic response to DNA modified by incorporation of anticancer nucleoside analogues. 1251 84

Indoleamine 2,3-dioxygenase (IDO) is an interferon-gamma (IFN-gamma)-induced enzyme, which is suggested to play an important role in the prevention of allogeneic fetal rejection. IDO effects the suppression of T-cell activity by catabolizing the essential amino acid l-tryptophan. We studied IDO expression by reverse transcription polymerase chain reaction (RT-PCR) in dendritic cells and by real-time RT-PCR in monocytes of patients undergoing allogeneic transplantation for leukaemia, who developed acute graft-versus-host disease (aGvHD), and compared the IDO expression with that of pregnant women and healthy volunteers. A spontaneous IDO expression was detected in the monocytes of 20 pregnant women with an IDO/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratio at a median of 1.0%, whereas none of 15 healthy volunteers or patients after allogeneic transplant had any detectable spontaneous IDO expression. The IDO expression increased by in vitro IFN-gamma stimulation in pregnant women (median 116%), healthy volunteers (median 11.7%) and patients with a low-grade aGvHD (grades 0-II) 28 days after transplant (median 433%) but not in patients with a severe aGvHD (grades III-IV) (median 0%), which was highly significant (P < 0.01). IDO expression was also measured in dendritic cells by qualitative RT-PCR, where a spontaneous IDO expression was detected in 16 of 31 (52%) pregnant women versus none of 17 healthy volunteers and none of 62 studied patients after transplant. IFN-gamma-induced IDO expression was detected in all pregnant women, all volunteers and 47 of 49 (96%) patients with a low-grade aGvHD (grades 0-II) after transplant, whereas only in two of 13 (16%) patients with aGvHD grade III-IV was IFN-gamma-induced IDO expression observed. These data suggest that IDO expression might be involved in the development of allogeneic immune tolerance.
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PMID:Indoleamine 2,3-dioxygenase expression in patients with acute graft-versus-host disease after allogeneic stem cell transplantation and in pregnant women: association with the induction of allogeneic immune tolerance? 1258 66


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