Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.26.9 (ribonuclease)
6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Particles with the density and enzymatic activity characteristic of known oncornavirus have been previously described in bone marrow cells from patients with leukemia in relapse and in remission. We have confirmed these findings and studied two patients in whom preleukemia was among the diagnostic considerations. Following cultivation of bone marrow from these patients for 1 week in conditioned media with dexamethasone, a high-speed pellet of the supernatant fluid and disrupted cells was prepared and analyzed on a sucrose gradient for enzymatic activity characteristic of RNA-directed DNA polymerase (reverse transcriptase). Peaks of endogenous DNA polymerase activity showing ribonuclease sensitivity and/or stimulation with the synthetic template poly(rC)-(dG)12-18 were demonstrated in both patients at densities of 1.15 to 1.19 and 1.21 to 1.24 g/ml. Subsequently, diagnosis 2 and 4 months after initial evaluation revealed acute myelogenous leukemia and malignant histiocytosis, respectively. Prior studies have suggested a possible etiological significance of such particles in human leukemia. The demonstration of similar particles preceding clinically overt disease in these patients supports this hypothesis and offers the possibility of early diagnosis and treatment.
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PMID:Oncornavirus-like particles from cultured bone marrow cells preceding leukemia and malignant histiocytosis. 5 58

This study is intended to establish biological correlation between the expression of lymphoid associated features in acute myeloid leukaemia (AML). In 62 AML patients, predominantly enrolled on Eastern Cooperative Oncology Group (ECOG) treatment protocols, in whom immunoglobulin (Ig) as well as T-cell receptor beta chain (TCR-beta) gene rearrangement analyses had been performed, morphology, cytochemistry, antigen profile and karyotype were reviewed retrospectively. Nuclear reactivity with anti-TdT antibody was demonstrated in 34 patients (55%) and confirmed by ribonuclease protection assay in all patients tested. Five TdT-protein negative patients were TdT-transcript positive. Lymphoid antigens (lyA) were detected in 24 of 51 cases tested (47%) with B-cell antigens (CD19, CD10) being restricted to TdT+ AML (P = 0.03). Only two patients had Ig heavy, none had Ig light chain or TCR-beta gene rearrangements. Although both patients with rearranged Ig loci were TdT+, either by protein or RNA analysis, the low incidence of such rearrangement within the TdT+ AML group (6%) argues against a significant association between the presence of TdT and crosslineage Ig gene rearrangements in AML. While FAB-diagnoses did not differ between TdT+ and TdT- or lyA+ and lyA- AML, particular immunophenotypic features correlated with TdT positively, e.g. the presence of early antigens, CD34 and HLA-DR, and the absence of the more mature myelo-monocytic antigens, CDw65 and CD14. Certain cytogenetic abnormalities were associated with TdT+ AML such as inv(16) (p13q22) or t(16;16) (p12;q22) (five patients; P = 0.03) and t(8;21) (q22;q22) (three patients). A greater number of TdT- than TdT+ AML patients had only normal karyotypes (P = 0.06). Neither immunophenotypic nor karyotypic correlations could be established for lyA+ AML.
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PMID:Lymphoid lineage-associated features in acute myeloid leukaemia: phenotypic and genotypic correlations. 141 14

Interferon-alpha (IFN) induces the enzyme 2-5 oligoadenylate synthetase (2-5 AS) in cells from patients with hairy cell leukemia and B-cell chronic lymphocytic leukemia and this is associated with a breakdown of certain species of cytokine messenger (m)RNA via the activation of a latent ribonuclease. We have studied the expression of the cytokines interleukin 1-beta (IL-1), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumour necrosis factor alpha (TNF) as well as of the ribonuclease activator 2-5 AS in the presence and absence of IFN in acute myeloid leukaemia (AML) blast cells from 26 patients. Before monocyte and T-cell depletion there was no expression of IL-1, IL-6 or GM-CSF, and only three of 13 patients studied expressed TNF mRNA. After cell depletion one or more cytokine was expressed in 31-62% of the 26 patients. Expression of one or more mRNA for IL-1, IL-6, GM-CSF and TNF after 18 h incubation was detected in 16 of 26 patients (63%) and this was particularly so in French-American-British (FAB) subtypes M4 and M5. Eight of nine patients with IL-6 mRNA expression and seven of 10 with IL-1 mRNA expression were in the FAB subtypes M4 and M5. Twenty-two of 26 patients showed induction of 2-5 AS mRNA in response to IFN in vitro. Exposure to IFN resulted in reduction of IL-1 mRNA in nine of 12 cases, of IL-6 mRNA in eight of nine, and GM-CSF mRNA in five of seven cases. TNF mRNA was unaffected by IFN despite 2-5 AS induction in 12 of 13 patients expressing this cytokine. In the presence of exogenous IFN, cells from six of seven patients studied showed inhibition of 3H-thymidine incorporation into DNA. DNA synthesis could also be abrogated in six of seven patients with anti-IL-1 monoclonal antibodies (MoAb) and in two of seven with anti-IL-6 MoAb. This inhibitory effect could be reversed in all patients when anti-IL-1 or anti-IL-6 was given in combination with their corresponding cytokine. These data suggest that IFN may exert a therapeutic effect in a proportion of AML patients by blocking IL-1 and IL-6 mediated growth, consequent on activation of the ribonuclease activator 2-5 AS.
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PMID:Effects of interferon-alpha (IFN) on the expression of interleukin 1-beta (IL-1), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF) in acute myeloid leukemia (AML) blasts. 143 98

Expression of the 93-kd tyrosine kinase encoded by the human c-fes proto-oncogene (also known as FES) is restricted to mature hematopoietic cells of the granulocytic and monocytic lineages, suggestive of a function essential to normal myeloid differentiation. However, recent studies have shown that c-fes can transform fibroblasts if sufficient levels of gene expression are achieved. These findings indicate that strict regulation of the c-fes gene is critical to normal myeloid development, whereas elevated c-fes expression may contribute to malignant transformation. In the present study, we compared the c-fes messenger RNA (mRNA) levels in leukemia blasts from patients with myeloid or lymphoid leukemia with those of peripheral monocytes from a normal donor with the use of a quantitative ribonuclease protection assay. The presence of c-fes mRNA was readily detected in both acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells, but c-fes mRNA was present in low levels or was absent in lymphoid leukemia cells. The leukemia cells of two of five AML patients and four of four CML patients expressed more c-fes mRNA than monocytes from a normal donor, with more than a threefold elevation in the cells of one CML patient. No evidence of amplification or rearrangement of the c-fes gene was detectable by Southern blot analysis of myeloid leukemia DNA, suggesting that the variation in c-fes mRNA levels are related to differences in transcriptional activity and/or message stability. These results indicate that elevated c-fes expression is a common feature of myeloid leukemia cells that could potentially contribute to the leukemia phenotype.
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PMID:Elevated expression of the c-fes proto-oncogene in adult human myeloid leukemia cells in the absence of gene amplification. 198 16

The clinical significance of serum ribonuclease (RNase) assay in acute leukemia was studied. Serum RNases were assayed by the method of Akagi et al. with slight modifications in the serum samples obtained from 50 cases of healthy subjects, 55 cases of acute leukemia before therapy, 18 chronic myelocytic leukemia before therapy, 13 chronic myelocytic leukemia under treatment and 20 reactive leukocytosis. The ratio of acid RNase to alkaline RNase activities (Ac/Al ratio) was statistically increased in acute promyelocytic leukemia, acute myeloblastic leukemia [M2], acute myelocytic leukemia and erythroleukemia (leukemic stage) compared with those in healthy subjects (P less than 0.001). All cases of acute promyelocytic leukemia and most of the acute myeloblastic leukemia [M2], acute myelomonocytic leukemia and erythroleukemia cases had an Ac/Al ratio of above 1.0. In remission of acute leukemia, it is noteworthy that acid and alkaline activities showed no substantial difference from those of healthy subjects. While, on relapse of acute leukemia cases, showing Ac/Al ratio above 1.0 in pretreatment state, Ac/Al ratio increased to above 1.0. Thus, the assay of serum RNases and the calculation of Ac/Al ratio might be an additional method for diagnosing acute leukemia and for assessing their remission and recurrence in some type of acute leukemia.
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PMID:[Clinical significance of serum ribonuclease (RNase) assay in acute leukemia]. 357 9

An RNA-directed DNA polymerase was isolated from the peripheral blood leukocytes of a patient with acute myelomonocytic leukemia by successive purification of a particulate cytoplasmic fraction with endogenous, ribonuclease-sensitive DNA polymerase activity. Like RNA-directed DNA polymerase from mammalian type-C virus, the human leukemic cell enzyme efficiently utilized (A)(n).(dT)(12-18) and (C)(n).(dG)(12-18) and had an approximate molecular weight of 70,000. Further, the leukemic cell enzyme was strongly inhibited by antisera to RNA-directed DNA polymerase of primate type-C virus in a fashion similar to that noted with an extensively purified RNA-directed DNA polymerase from a person with acute myelogenous leukemia [Todaro, G.J. & Gallo, R.C. (1973), Nature 244, 206]. By these biochemical and immunological results the leukemic cell enzyme could be differentiated from all other known cellular DNA polymerases but could not be distinguished from RNA-directed DNA polymerase of primate type-C virus. We interpret these data, combined with observations published elsewhere, to indicate that human acute myelogenous leukemia cells contain components related to primate type-C virus. The parameters used in this study may provide the specificity and sensitivity required for determining the presence or absence and (if present) the relatedness of RNA-directed DNA polymerase in other cases and types of human leukemia.
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PMID:Relationship between RNA-directed DNA polymerase (reverse transcriptase) from human acute leukemic blood cells and primate type-C viruses. 413 50

A somatic translocation event fusing the novel gene set to the putative oncogene can has been implicated in the development of acute nonlymphocytic leukemia in humans. In this study, full-length cDNAs highly homologous with human set were cloned from a rat neonatal kidney library. The expression pattern of set mRNA was then examined in developing rat kidney. Two groups of set cDNAs (alpha and beta) with different translation initiation sites and open reading frames of 867 and 831 bp, respectively, were found. The predicted protein products are 33,385 and 32,085 Da in size and contain approximately 30% acidic residues, over half of them clustered at the COOH terminal, thus forming a long acidic tail. No signal peptide or membrane-spanning domains were identified, suggesting an intracellular protein product. By ribonuclease protection assay, both alpha and beta variants of set were expressed in kidney. On Northern blots of total kidney RNA, 3.0- and 2.2-kb mRNAs hybridized with the labeled set cDNA probe. Expression of both transcripts was four- to eightfold greater in neonatal compared with adult rat kidney. When neonatal rat kidneys were examined for set mRNA expression by in situ hybridization with 35S-labeled riboprobe, expression was densely localized in the cortical region of morphogenesis over primitive nephron structures, including S-shaped bodies. Thus mRNA for Set, a putative intracellular protein involved in leukemogenesis, is expressed in kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spatially restricted expression of set mRNA in developing rat kidney. 750 4

We examined whether the allegedly aberrant expression of the lymphoid lineage associated DNA polymerase, terminal deoxynucleotidyl transferase (TdT), in acute myeloid leukaemia (AML) is associated with alterations of the enzyme at the cellular, biochemical or transcriptional level when compared to lymphoid leukaemia (ALL), either lacking or expressing myeloid antigens. By flowcytometric analysis, the intensity of TdT staining with monoclonal anti-TdT antibody was considerably weaker in TdT+ AML and myeloid+ ALL (M+ ALL) than in myeloid- ALL (M- ALL). TdT enzyme activity in TdT+ AML was on an average 10%, and in M+ ALL 25% of that measured in M- ALL. Anti-TdT antibodies precipitated a major specific protein of identical relative molecular mass (58 kD) from metabolically labelled TdT+ myeloblasts and lymphoblasts. By Northern blot analysis and ribonuclease protection assay, TdT transcript levels were significantly lower in TdT+ myeloblasts and M+ lymphoblasts than in M- ALL (P < 0.0001). The level of TdT transcription in AML was independent of the simultaneous expression of lymphoid-specific antigens, such as CD2 and CD19. Our data demonstrate that TdT expression is downregulated in association with myeloid features, not only in AML but also in ALL. This observation may provide the molecular basis for the differential therapeutic responsiveness, particularly to glucocorticoids, in these various leukaemia subtypes.
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PMID:Differential expression of terminal transferase (TdT) in acute lymphocytic leukaemia expressing myeloid antigens and TdT positive acute myeloid leukaemia as compared to myeloid antigen negative acute lymphocytic leukaemia. 821 92

Cell surface levels of the receptor tyrosine kinase P145(c-kit), the product of the c-kit proto-oncogens, in a panel of 80 primary adult acute myeloid leukaemia (AML) specimens collected at presentation were quantitated by immunofluorescence and flow cytometry, and compared with levels on CD34+ bone marrow cells from normal donors. Receptor levels on AML blast cells were extremely variable and were similar to, or less than, those on normal stem and progenitor cells. In general P145(c-kit) expression was higher on cells of immature phenotype (FAB M1 and M2). c-kit mRNA was quantitated by ribonuclease protection assay (RPA) and was shown to be correlated with cell surface protein expression (r=0.76; P<0.001). This indicates that ligand-mediated receptor internalisation or other mechanisms of increased protein turnover are not responsible for variations in the level of P145(c-kit) in AML specimens. Quantitative Southern blotting was used to examine c-kit gene copy number in 25 of these specimens and was found to be normal in all but one. Thus we have found little evidence of over-expression of c-kit in adult AML. mRNA for the c-kit ligand, Steel Factor (SLF) was also quantitated by RPA in these specimens. While SLF message was detectable (limit of detection approximately 10(4) copies per 10 microgram total RNA; equivalent to 1 copy per 100 cells) in 19% of cases, these specimens in general contained low levels of c-kit mRNA. Thus, an autocrine cycle involving c-kit and SLF does not appear to be a common feature of AML.
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PMID:Increased expression of c-Kit or its ligand Steel Factor is not a common feature of adult acute myeloid leukaemia. 863 38

Acute myeloid leukemia is the most common acute leukemia affecting adults, and its incidence increases with age. Along with chromosomal translocations in leukemic cells mutations in the genes of receptor tyrosine kinases KIT and FLT3 were found with a high frequency. Here we show that transgenic progenitor of B-cells BAF3/FLT3-ITD are much more sensitive to the ribonuclease binase cytotoxic effects than the original BAF3 cells. The principal difference between BAF3/FLT3-ITD and the original BAF3 cells is the expression of FLT3-ITD oncogene, which leads to a change in the normal cell signaling pathways. Earlier, we described a similar effect for the cytotoxic action of binase on Kasumi-1 and FDC-P1-N822K cells, which express the activated KIT-N822K oncogene. Increased binase cytotoxicity toward the cells, expressing FLT3-ITD oncogene, suggests that, as in the case of FDC-P1 cells, transduced by KIT oncogene, the expression of an activated oncogene determines the sensitivity of cells to binase.
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PMID:[Expression of FLT3-ITD oncogene confers mice progenitor B-cells BAF3 sensitivity to the ribonuclease binase cytotoxic action]. 2380 62


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