Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The red alga, Agardhiella tenera was found to contain a glycoprotein which agglutinates mouse leukemia cells, L5178Y but not L1210. It also agglutinates guinea pig and rabbit erythrocytes, and has weak activity against human A, B and O, mouse, horse and sheep erythrocytes and hamster and mouse lymphocytes. The agglutination was not inhibited by simple sugars. The major active component was purified and determined to be a beta-structure protein containing 2.7% glucose as sugar moiety. The molecular weight was estimated to be 12,000 by gel filtration and 13,000 by polyacrylamide gel electrophoresis, in the presence of sodium dodecylsulfate. Its isoelectric point was 6.1, and it contained high amounts of glycine, serine and threonine, but no half cystine or histidine. It had no subunit structure, and the C- and N-terminal amino acids were threonine and arginine, respectively.
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PMID:Purification and characterization of an agglutinin in the red alga Agardhiella tenera. 76 Aug 1

Covalent DNA-protein crosslinks occur in exponentially growing mouse leukemia cells (L1210) after exposure to ionizing radiation. The amount of DNA-protein crosslinks as measured by a filter binding assay is dose dependent upon X irradiation. Although hyperthermia and radiation in combination are synergistic with respect to cell lethality, the combination does not result in an increase of DNA-protein crosslinks when assayed immediately following treatments. Hyperthermia (43 degrees C/15 min) given prior to radiation does not alter the radiation dose dependency of the amount of initial crosslinking. In addition, the amount of DNA-protein crosslinking produced by heat plus radiation is independent of the length of heating the cells at 43 degrees C. The DNA-protein crosslinks produced by 50-Gy X ray alone are removed after 2 hr at 37 degrees C. However, if hyperthermia (43 degrees C/15 min) is given prior to 100-Gy X ray, the removal of DNA-protein crosslinks is delayed until 4.0 hr after radiation. Phospho-serine and phospho-threonine bonds are not produced with either radiation or the combination of hyperthermia plus radiation as judged by the resistance of the bonds to guanidine hydrochloride. However, hyperthermia plus radiation causes an increase in phosphate to nitrogen type bonding. These results show that radiation alone causes covalent DNA-protein crosslinks. Hyperthermia in combination with radiation does not increase the total amount of the crosslinks but delays the removal of the crosslinks and alters the distribution of the types of chemical bonding. These data suggest that the synergistic action on hyperthermia with radiation is more related to the rate of removal and the type of chemical bonding involved in the covalent DNA-protein crosslinks rather than the amount of DNA-protein crosslinks.
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PMID:Covalent DNA-protein crosslinking occurs after hyperthermia and radiation. 661 65

We generated variants of the human immunodeficiency virus type 1 (HIV-1) that are resistant to 2',3'-dideoxycytidine (ddC) and 2',3'-didehydro-3'-deoxythymidine (d4T) by in vitro selection in MT-4 cells. Portions of flanking protease and integrase sequences as well as the complete reverse transcriptase (RT) open-reading frame of these viruses were cloned and sequenced, using polymerase chain reaction (PCR)-based methods. Mutations were observed at amino acid position 65 (Lys-->Arg; AAA-->AGA) when ddC was employed in the selection procedure and at site 50 (Ile-->Thr; ATT-->ACT) when d4T was used. We confirmed the ability of these mutations to confer diminished sensitivity for these compounds by site-directed mutagenesis, in which these mutations were inserted into the pol gene of infectious recombinant HXB2-D DNA. Viruses that contained the site 65 mutation possessed approximately 5-10 fold resistance against ddC when compared with wild-type HXB2-D. The site 50 mutation conferred approximately 30-fold resistance to d4T in these same assays. Similar results were obtained using primary cord blood lymphocytes in drug resistance assays, indicating that these mutations could confer drug resistance in more than one cell type and that the respective mutations could be expressed in cells of primary origin. No cross-resistance against 3'-azido-3'-deoxythymidine (AZT) was noted for either the site 65 or 50 mutations.
Leukemia 1994 Apr
PMID:Identification of novel mutations that confer drug resistance in the human immunodeficiency virus polymerase gene. 751 78

Interleukin-6 is a multifunctional cytokine which regulates various aspects of the host immune response. Here we show that signaling events transferred by IL-6 in monocytes and the U937 human monocytic leukemia cell line lead to the phosphorylation of the small heat shock protein (Hsp)27. Phosphorylation of Hsp27 is both dose- and time-dependent. In the absence of NaF, a serine/threonine phosphatase inhibitor, IL-6 failed to initiate Hsp27 phosphorylation in vitro. IL-6 also failed to phosphorylate Hsp27 when cells had been deactivated with tyrosine kinase inhibitors such as genistein. The capacity of cellular extracts to phosphorylate Hsp27 could be, however, restored when either immunoprecipitated activated MAP kinase or purified MAPKAP kinase 2 was added to cell lysates. These findings suggest that IL-6-mediated phosphorylation of Hsp27 results from activation of MAPKAP kinase 2, a serine/threonine kinase which is activated by MAP kinase. Taking together, our findings indicate that IL-6-induced activation of MAP kinase by IL-6 entails the activation of MAPKAP kinase 2 and subsequent phosphorylation of the Hsp27.
Leukemia 1995 Feb
PMID:Interleukin (IL)-6 signaling leads to phosphorylation of the small heat shock protein (Hsp)27 through activation of the MAP kinase and MAPKAP kinase 2 pathway in monocytes and monocytic leukemia cells. 786 66

The Pim-1 gene has frequently been found activated by proviral insertion in haematopoietic tumors in mice. The fact that overexpression of Pim-1 can contribute to lymphomagenesis was formally proven by overexpressing a Pim-1 transgene in lymphoid cells. The transgene induces a low incidence of T cell lymphomas and an increased susceptibility to chemically (ENU) and virally (MoMuLV) induced lymphomas. The mouse Pim-1 gene encodes two cytoplasmic protein-serine/threonine kinases. Northern analysis shows the highest expression to be in haematopoietic tissues, especially early in development. High expression has also been noted in testis and ES cells. Expression can be induced by growth factors and mitogens. The gene is evolutionarily highly conserved. Inactivation of both Pim-1 alleles in ES cells or mice did not reveal any obvious abnormalities. In order to look more closely for possible haematopoietic abnormalities specific growth factor response were studied in vitro. The IL-3 response of bone marrow-derived mast-cell cultures (BMMC) was found to be severely impaired in mast cells derived from Pim-1 deficient mice.
Leukemia 1993 Aug
PMID:Analysis of Pim-1 function in mutant mice. 836 Dec 11

The intracytoplasmic tail of the granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) beta c chain is essential for the activation of ligand-mediated signal transduction pathways in myeloid cells. Alterations in this region could deregulate normal signalling processes. We have therefore used RT-PCR-SSCP analysis of the receptor tail to look for point mutations in RNA from 35 patients with acute myeloid leukaemia (AML) and 10 haematologically normal controls. Patterns differing from those of the haemopoietic cell line TF-1 were detected in 25/35 (71%) AML patients and 8/10 (80%) normal controls. A total of six base substitutions were identified by sequencing. Three were conservative for the amino acid involved, three led to amino acid differences, valine652-->methionine, glycine647-->valine and proline603-->threonine. One alteration was found only in a normal control, the other five were all found in both AML patients and normal controls suggesting that they were DNA polymorphisms. Two substitutions were particularly common with allele frequencies of 0.23 (G1972-->A, unchanged proline648) and 0.13 (C1306-->T, unchanged serine426). These results indicate that the GM-CSFR beta c chain is highly polymorphic but point mutations of the intracytoplasmic tail do not appear to contribute frequently to the pathogenesis of AML.
Leukemia 1996 Jan
PMID:The beta subunit common to the GM-CSF, IL-3 and IL-5 receptors is highly polymorphic but pathogenic point mutations in patients with acute myeloid leukaemia (AML) are rare. 855 16

The cell cycle has been the object of extensive studies for the past years. A complex network of molecular interactions has been identified. In particular, a class of cell cycle inhibitory proteins has been cloned and characterized but details of the molecular mechanism of their action have yet to be resolved. These inhibitors regulate the progression through G1 and the G1/S transition via the inhibition of the cyclin-dependent kinase (Cdk) activity. The potential function of these negative regulators as tumor suppressors provides new insights into the link between the cell cycle and oncogenesis. p27 is a potent inhibitor of Cdks. In quiescent cells p27 accumulates without an increase in mRNA or protein synthesis. Cell cycle regulation of p27 levels, both in normal and transformed human cells, occurs via the ubiquitin-proteasome pathway and, compared to proliferating cells, quiescent cells contain a far lower amount of p27 ubiquitinating activity. The specific proteolysis of p27 is probably involved in the pathway of activation of Cdks. p27 is a phosphoprotein and its phosphorylation is cell cycle regulated. Often phosphorylation is a signal for ubiquitination. p27 is phosphorylated exclusively on serine by Erk1 and almost exclusively on threonine by Cdk1 in in vitro experiments. This finding raises the question of whether and how phosphorylation by these kinases is involved in the process of p27 proteolysis.
Leukemia 1997 Mar
PMID:Regulation of the cyclin-dependent kinase inhibitor p27 by degradation and phosphorylation. 906 71

Okadaic acid, an inhibitor of serine/threonine protein phosphatases 1 and 2A has been shown to cause mitotic arrest and cell death of HL-60 and K562 cells. HL-60 cells express Bcl-2 and little or no Bcl-X(L), while K562 expresses Bcl-X(L) but not Bcl-2. Since phosphorylation/dephosphorylation reactions have been suggested to be involved in the regulation of Bcl-2, we planned to investigate whether the expression of Bcl-2, Bcl-X(L) and Bax, a protein that antagonizes the antiapoptotic function of Bcl-2, are regulated in myeloid leukemia cell lines (K562, KU812 and HL-60) treated with okadaic acid. Our results indicate that exposure of all three leukemic cell lines to nanomolar concentrations of okadaic acid causes a loss of viability by activation of an apoptotic process accompanied by a marked decrease in the expression of Bcl-2, Bcl-X(L) and Bax at both mRNA and protein level, but not of c-fos, vimentin and epsilon-globin, ruling out a non-specific effect of okadaic acid. Furthermore, constitutive expression of either Bcl-X(L) or Bcl-2 by gene transfer inhibited apoptosis triggered by okadaic acid in K562 cells. Thus, we suggest that protein phosphatases may be involved in maintaining the expression of bcl-2 family genes as part of the survival machinery of the cell.
Leukemia 1997 Jul
PMID:Apoptosis of human myeloid leukemia cells induced by an inhibitor of protein phosphatases (okadaic acid) is prevented by Bcl-2 and Bcl-X(L). 920 72

The AML1 is the most commonly involved transcription factor gene in human leukemias and forms chimeric transcription factor genes, namely, AML1/MTG8 by the t(8;21), AML1/EVI-1 by the t(3;21), and TEL/AML1 by the t(12;21). The AML1a and AML1b, two isoforms of the AML1 protein, are translated from the AML1 gene by the alternative splicing. The shorter form and longer form are named as AML1a and AML1b, respectively. The AML1b contains the runt homology domain as a DNA-binding domain and the serine/proline/threonine-rich domain (PST domain) as a putative transactivation domain. The AML1a contains only the runt homology domain, but not the PST domain. The AML1b has a transactivation ability through the PEBP2 site and stimulates differentiation of myeloid cells. On the other hand, AML1a cna bind the PEBP2 site, but does not show a transactivation ability through the PEBP2 site. The AML1a dominantly suppresses transactivation induced by the AML1b and has the ability to block differentiation of myeloid cells. It is a reasonable hypothesis that the molecular ratio of AML1a to AML1b in myeloid cells could determine whether they proliferate or undergo a terminal differentiation.
Leukemia 1997 Apr
PMID:Leukemogenesis by the chromosomal translocations. 920 70

MTG8 is a counterpart gene of AML1 in acute myeloid leukemia with t(8:21) translocation. Most of the coding region of the MTG8 is fused with AML1 runt domain. In normal tissues, the MTG8 is highly expressed in brain, but not in hematopoietic tissues. MTG8 may be important in leukemogenesis as well as in AML1 truncation. The function of MTG8 is assumed to be as a transcription factor, because it possesses several features common to transcription factors; putative zinc finger motifs, serine/threonine/proline-rich sequences and a region similar to TAF110. In this paper, we report on the protein properties of the MTG8.
Leukemia 1997 Apr
PMID:Significance of MTG8 in leukemogenesis. 920 71


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