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)

To investigate whether there are NUP98-HOXA, NUP98-HOXB, NUP98-HOXC, NUP98-HOXD fusion genes in leukemia patients in Xinjiang, cellular total RNA was extracted from the bone marrow mononuclear cells, the formaldehyde-agarose gel electrophoresis was used to judge whether RNA was intact, the 17 RT-PCR primers were designed to amplify the predicted fusion junctions and 412 bp GAPDH was used as an internal control, NUP98-HOXA fusion genes were amplified by nested-PCR following reverse transcription. One-step PCR was performed to amplify the other predicted fusion genes. The results showed that RNA was proved to be intact and expression of GAPDH was found in every sample. However, no predicted fusion transcripts were detected in leukemia patients. In conclusion, no NUP98-HOX fusion genes were detected in the samples from Xinjiang.
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PMID:[RT-PCR detecting NUP98-HOX fusion gene in leukemia]. 1574 41

Resistance to glucocorticoids (GC) is an important adverse risk factor in the treatment of acute lymphoblastic leukemia (ALL). To induce apoptosis, GC bind to the GC receptor (GR), which is regulated by various (co)chaperone proteins such as heat-shock protein 70 (HSP-70), HSP-40, HIP (HSP-70-interacting protein), BAG-1 (BCL-2-associated gene product-1), HOP (HSP-70/HSP-90-Organizing protein), HSP-90, P-23, FKBP-51, FKBP-52 and CYP-40. In this study, we tested the hypothesis that mRNA expression levels of these molecules are determinants of GC resistance in childhood ALL. In all, 20 children with ALL cells in vitro sensitive to prednisolone (LC(50) < 0.1 microg/ml) were compared each with a resistant patient (LC(50) >150 mug/ml), matched for immunophenotype, age and white blood cell count. mRNA expression levels of the (co)chaperone molecules were measured by quantitative real-time RT-PCR and normalized to GAPDH and RNaseP levels. In vitro resistance to prednisolone was measured by MTT assay. HSP-90 mRNA expression levels were 2000-fold higher as compared to HSP-70. Using matched pair analysis, mRNA expression levels of the various (co)chaperone molecules were not significantly different between in vitro-sensitive and -resistant patients. GC resistance in childhood ALL cannot be attributed to different mRNA expression levels of the investigated (co)chaperone molecules involved in GC binding and transport to the nucleus.
Leukemia 2005 May
PMID:mRNA expression levels of (co)chaperone molecules of the glucocorticoid receptor are not involved in glucocorticoid resistance in pediatric ALL. 1575 36

Neuroblastoma (NB) is the most common malignant solid tumor in childhood, and among all childhood malignancies is second in prevalence only to leukemia. In NB we need to both make an accurate diagnosis and rapidly analyze the expression of genetic prognostic factors such as MYCN, H-ras, and trkA. Moreover, it has recently become important to analyze the expression of survivin mRNA, a member of the inhibitor of apoptosis protein family. Expression of the survivin gene is related to tumorigenesis and inhibition of apoptosis in some malignant tumors. We investigated its expression by reverse transcription-polymerase chain reaction (RT-PCR) in NB cell lines (SK-N-SH, NB-39, and IMR-32), two normal blood cell samples, and 13 clinical NB tumor samples. All three NB cell lines had high levels of mRNA expression for this gene, but normal blood cells had no expression. We detected expression of survivin mRNA in 7 of the 13 NB tumor samples (54%). Two NB patients were in stage I disease, 6 in stage II, and 5 in stage IV(A). Quantitative analysis by RT-PCR revealed that the ratio between survivin mRNA and human glyceraldehyde-3-phosphate dehydrogenase (h-GAPDH) mRNA was very low in stages I and II (0-0.017). In contrast, in advanced NBs (stage IV(A)) the ratio was much higher (0-0.050). The prognoses of the three patients in the advanced stage who had high ratios of expression were poor. A high level of expression of survivin mRNA indicates a high grade of malignancy, high likelihood of recurrence, and poor prognosis.
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PMID:Significance of survivin mRNA expression in prognosis of neuroblastoma. 1580 87

This study attempts to identify a suitable endogenous control gene for real-time RT-PCR in nonsmall cell lung cancer (NSCLC) tissues. Expression of seven common endogenous control genes (glyceraldehyde-3-phosphate dehydrogenase (GAPDH), v-abl Abelson murine leukaemia viral oncogene homologue 1, beta-2-microglobulin, hypoxanthin phosphoribosyltransferase 1 (HPRT1), phosphoglycerate kinase 1, peptidylprolyl isomerase A, and ribosomal protein, large, P0) in 18 heterogenous NSCLC tumour specimens, 10 normal lung tissues and six NSCLC cell lines were analysed by quantitative RT-PCR. The variances and correlation coefficients of cycle threshold (Ct) value of each control gene in three tissue groups and subgroups were compared. The difference and correlation coefficients between the Ct value for each control gene and the mean Ct value of the remaining control genes were calculated. The GAPDH gene transcript showed the least variance and linear regression analysis demonstrated that GAPDH and HPRT had the strongest correlation in pooled tumour and normal lung tissues. Furthermore, GAPDH expression value showed stringent correlation and had the lowest difference with the mean expression value of the remaining endogenous control genes. Among the seven common endogenous control genes, glyceraldehyde-3-phosphate dehydrogenase is the most suitable for quantitative RT-PCR reaction in nonsmall cell lung cancer tissue samples.
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PMID:Choice of endogenous control for gene expression in nonsmall cell lung cancer. 1631 28

The interleukin-3 receptor (IL-3R) subunits are overexpressed on acute myeloid leukemia (AML) blasts compared with normal hematopoietic cells and are thus potential targets for novel therapeutic agents. Both fluorescence-activated cell sorter (FACS) analysis and quantitative real-time reverse transcription-polymerase chain reaction (QRT-PCR) were used to quantify expression of the IL-3Ralpha and beta(c) subunits on AML cells. QRT-PCR for both subunits was most predictive of killing of AML colony-forming cells (AML-CFCs) by diphtheria toxin-IL-3 fusion protein (DT(388)IL3). Among 19 patient samples, the relative level of the IL-3Ralpha was higher than the IL-3Rbeta(c) and highest in CD34(+)CD38(-)CD71(-) cells, enriched for candidate leukemia stem cells, compared with cell fractions depleted of such progenitors. Overall, the amount of IL-3Rbeta(c) subunit did not vary among sorted subpopulations. However, expression of both subunits varied by more than 10-fold among different AML samples for all subpopulations studied. The level of IL-3Rbeta(c) expression versus glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (set at 1000) ranged from 0.14 to 13.56 in CD34(+)CD38(-)CD71(-) cells from different samples; this value was correlated (r = .76, P = .05) with the ability of DT(388)IL3 to kill AML progenitors that engraft in beta(2)-microglobin-deficient nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice (n = 7). Thus, quantification of IL-3R subunit expression on AML blasts predicts the effectiveness IL-3R-targeted therapy in killing primitive leukemic progenitors.
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PMID:Expression of interleukin-3 receptor subunits on defined subpopulations of acute myeloid leukemia blasts predicts the cytotoxicity of diphtheria toxin interleukin-3 fusion protein against malignant progenitors that engraft in immunodeficient mice. 1688 9

Peroxiredoxins (Prx) comprise an extended family of small antioxidant proteins which conserve a thioredoxin-dependent catalytic function that can contribute to cell protection from reactive oxygen species (ROS). ROS generation is one of the deleterious intracellular effects of ionizing radiation, but the role of Prx during radiation treatment has not been extensively explored. Present experiments measure effects of ionizing radiation on expression of human Prx types I (PAGA), II (NKEF-B) and IV (AOE372) in human myeloid leukemia cells (K562). Prx gene transcription was analyzed by amplifying with RT-PCR cDNAs complementary to each Prx-specific coding sequence and by identifying the derived products with Southern blotting procedure. Transcripts of GAPDH were used as the endogenous standard for semi-quantitative comparisons. No consistent increase in Prx gene expression was detected at time intervals up to 72 h after gamma radiation doses that caused cell cycle arrest and nuclear damage (maximum 20 Gy). Immunoblots also were consistent with a prolonged expression or stability of the Prx I/II proteins. Similarly, a cytotoxic concentration of the oxidant hemin, which stimulates rapid hemoglobinization of K562 cells, caused no induction of Prx gene expression. Our results indicate a high Prx stability in human radio-resistant leukemia cells.
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PMID:Peroxiredoxin genes are not induced in myeloid leukemia cells exposed to ionizing radiation. 1702 36

Regulators of G protein signalling (RGS) are involved in the negative regulation of cell activation processes and are involved in the pathophysiology of cardiovascular diseases. To get some further evidence for a role of RGS proteins in platelets, we determined the expression profile of RGS-specific mRNA in rat platelets using reverse transcription-polymerase chain reaction (RT-PCR) with a poly dT18 primer and transcript-specific primers. We found that RGS2, RGS3, RGS5, RGS6, RGS10, RGS14, RGS16 and RGS18, Leukemia-associated Rho-GEF factor (LARG), and Galpha interacting protein (GAIP) were differentially expressed in platelets. The highest expression rate was found for RGS18 (about 1.3 fold when compared to GAPDH), followed by LARG, RGS6, RGS10 and RGS16 (0.7 to 0.95), whereas expression rates for RGS2, RGS3, RGS5, RGS14, and GAIP were in a range of 0.1 to 0.3. Our results suggest that G-protein-coupled receptor-mediated signalling in platelet may be regulated mainly by RGS 18, 16, 10, 6, and LARG.
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PMID:The expression patterns of RGS transcripts in platelets. 1707 26

The degree to which gene expression covaries between different primary tissues within an individual is not well defined. We hypothesized that expression that is concordant across tissues is more likely influenced by genetic variability than gene expression which is discordant between tissues. We quantified expression of 11,873 genes in paired samples of primary leukemia cells and normal leukocytes from 92 patients with acute lymphoblastic leukemia (ALL). Genetic variation at >500,000 single nucleotide polymorphisms (SNPs) was also assessed. The expression of only 176/11,783 (1.5%) genes was correlated (p<0.008, FDR = 25%) in the two tissue types, but expression of a high proportion (20 of these 176 genes) was significantly related to cis-SNP genotypes (adjusted p<0.05). In an independent set of 134 patients with ALL, 14 of these 20 genes were validated as having expression related to cis-SNPs, as were 9 of 20 genes in a second validation set of HapMap cell lines. Genes whose expression was concordant among tissue types were more likely to be associated with germline cis-SNPs than genes with discordant expression in these tissues; genes affected were involved in housekeeping functions (GSTM2, GAPDH and NCOR1) and purine metabolism.
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PMID:Concordant gene expression in leukemia cells and normal leukocytes is associated with germline cis-SNPs. 1847 92

Tumour suppressor protein p53 prevents cancer development through various mechanisms, including the induction of apoptosis. We demonstrated that acute leukaemia, myeloblastic (AML) and lymphoblastic (ALL), is associated with significantly elevated levels of p53 and Bax mRNA in leukaemic cells. Regarding ALL, significantly elevated levels of Bcl-xL mRNA may explain the relative resistance of ALL cells to p53-dependent apoptosis. Altered alternative processing of Bcl-x and myeloid cell leukaemia-1 (MCL1) primary transcripts were observed in the case of AML and AML and ALL, respectively. We assumed that increased glyceraldehyde-3-phosphate dehydrogenase (gapdh) transcription and decreased MCL1s mRNA were not fully responsible for the dysregulation of p53-dependent apoptosis in the case of AML. In addition, transcription of hsp70.1 and Bcl-2 producing anti-apoptotic proteins was not affected in acute leukaemia.
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PMID:Transcription of genes of p53-dependent apoptosis in acute leukaemia. 1902 Jul 83

Biologic characterization of SB-559457 (SB), a nonpeptidyl hydrazone class of thrombopoietin receptor (Mpl) agonist, revealed toxicity toward human leukemia cells. Antiproliferative effects followed by significant, nonapoptotic, cell death within 72 hours occurred in 24 of 26 acute myeloid leukemia, 0 of 6 acute lymphoblastic leukemia, and 3 of 6 chronic myeloid leukemia patient samples exposed to SB, but not recombinant human thrombopoietin (rhTpo), in liquid suspension culture. Further investigation revealed increased phosphorylation of p70S6/S6 kinases in SB-, but not in rhTpo-, treated cells. Expression profiling of cells exposed to SB versus rhTpo revealed statistically significant, more than 2-fold changes in GAPDH and REDD1 gene expression, confirmed by quantitative reverse-transcribed polymerase chain reaction. These genes, induced in energy or hypoxia stressed cells, have been implicated in cell death pathways, and may provide important clues to the mechanism of SB-induced, leukemic cell death. These results suggest that nonpeptidyl, hydrazone class Mpl agonists may be clinically useful antileukemic agents by virtue of their combined thrombopoietic and antileukemic effects.
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PMID:A prototype nonpeptidyl, hydrazone class, thrombopoietin receptor agonist, SB-559457, is toxic to primary human myeloid leukemia cells. 1988 Apr 92


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