Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult T cell leukemia-derived factor (ADF) is a human thioredoxin (Trx) and is a disulfide reducing protein with various biological functions. We found that expression of the ADF/Trx gene was increased by oxidative agents such as hydrogen peroxide, diamide and menadione in Jurkat cells. Analysis using a CAT expression vector plasmid under the control of the ADF/Trx gene promoter revealed that CAT gene expression in Jurkat cells was increased after exposure to oxidative agents. A series of deletion analyses showed that a region from -976 to -890 of the 5' flanking sequence was required for enhancement of ADF/Trx promoter activity against the oxidative agents. Gel mobility shift assay revealed the specific DNA binding activities to the sequences from -953 to -930 in the nuclear extracts from the Jurkat cells. The sequences in this region showed no homology with any known consensus sequences for DNA binding factors. It is suggested that ADF/Trx gene expression is enhanced through a novel cis-acting regulatory element responsive for the oxidative stress and a new factor(s) is involved in this oxidative stress responsive element.
 ...
PMID:A novel promoter sequence is involved in the oxidative stress-induced expression of the adult T-cell leukemia-derived factor (ADF)/human thioredoxin (Trx) gene. 875 6

We compared the efficiency of human immunodeficiency virus (HIV-1) vectors that express a marker gene (chloramphenicol acetyltransferase, CAT) using different promoter elements. In one vector, CAT was expressed under the control of an internal murine leukemia virus (MuLV) long terminal repeat (LTR). In other vectors, CAT production was regulated by the HIV-1 LTR; these vectors also contained the HIV-1 tat gene and pol sequences reported to exert cis-acting positive effects on reverse transcription or gene expression. Vectors employing the Tat-driven HIV-1 LTR exhibited up to 500-fold greater CAT expression in Jurkat lymphocytes or human peripheral blood mononuclear cells compared with vectors using the internal MuLV LTR element as a promoter. This difference was not due to improved packaging of the vector RNA into virions, but to an improved level of gene expression in the target cells. Target cell CAT expression was two- to threefold higher for the vector containing the pol sequences and was only slightly less than that seen for a trans-complemented envdeleted provirus. These results indicate that defective HIV-1 vectors with efficiencies of gene transfer and expression comparable with that of HIV-1 itself are feasible.
 ...
PMID:Use of cis- and trans-acting viral regulatory sequences to improve expression of human immunodeficiency virus vectors in human lymphocytes. 880 25

The expression of the human myeloid zinc finger gene (MZF-1) by human bone marrow cells is necessary for granulopoiesis. We have analyzed the structure and function of the MZF-1 gene by diagnostic polymerase chain reaction, genomic cloning, and promoter analysis. Comparison of human promyelocytic HL-60 cell cDNA with isolated MZF-1 genomic clones indicated that the human MZF-1 gene is without introns and spans approximately 3 kb. Restriction enzyme mapping and Southern analysis indicated further that the human MZF-1 gene is a single-copy gene. Primer extension studies identified the major transcription start site as a thymidine residue located 1102 bp upstream of the ATG translation start codon. A putative TATA box sequence (TAAAAA) was found at -66 bp and a CCAAT box at -130 bp relative to the transcription initiation site. In HL-60 cells, MZF-1 mRNA levels are increased by granulopoietic inducers including retinoic acid and GM-CSF. DNA upstream of the transcription start site contains tandem-repeated consensus retinoic acid response elements at -666 through -696 bp and paired putative GM-CSF-responsive sequences centered at -50 and -100 bp. CAT reporter gene constructs containing these DNA regions promoted transcription and conferred transcriptional responsiveness to retinoic acid and GM-CSF when transfected into HL-60 cells. Additional putative regulatory binding sites included conserved MZF-1 zinc finger binding sequences, the importance of which was suggested by the enhanced expression of the endogenous MZF-1 gene following vector-driven expression of MZF-1 constructs in K562 myeloblastic leukemia cells. These findings provide a clearer basis for understanding the role of MZF-1 gene expression in myeloid cell growth and differentiation.
 ...
PMID:Isolation and functional characterization of the human gene encoding the myeloid zinc finger protein MZF-1. 884 78

Mucormycosis (zygomycosis) is an uncommon mycosis which can be contracted from the environment and which is responsible for rhino-orbital, pulmonary, gastrointestinal, cerebral or disseminated infections. Severe immunodepression, such as that caused by leukemia, lymphomata and organ graft, or treatment by desferrioxamine, may predispose to pulmonary and systemic forms. In the present work the authors describe a case of systemic mucormycosis, with unfavourable outcome, which arose in a pediatric peritoneal dialysis patient, then transferred to hemodialysis, without evident predisposing factors. In particular they refer to the CAT reports and to lymphonodal and peritoneal histological lesions which allowed them to attain the diagnosis.
 ...
PMID:[Systemic mucormycosis in dialysis: computed tomography picture and histologic lesions]. 884 70

Using the human T-cell leukemia virus type I (HTLV-I) infected SLB-I T-cell line, we showed in this study that 5-d treatment with the maximal subtoxic 3-methylcholanthrene (3-MC) dose (0.25 microgram/ml), as well as with a 3-MC dose that inhibits 50% of the cell growth (5 micrograms/ml), profoundly increased the level of viral RNA. Exposure to these 3-MC doses for 5 d before transient transfection of HTLV-I LTR-CAT construct into these cells markedly stimulated CAT activity, indicating that 3-MC exerted its effect by a trans-acting mechanism. A similar stimulation was observed when this construct was transfected into 3-MC treated uninfected Jurkat cells, indicating that this trans-acting effect was independent of the viral tax protein. However, although the subtoxic 3-MC dose increased also the capacity of SLB-I cells to transmit the virus to normal peripheral blood lymphocytes in coculture, the toxic dose strongly reduced this capacity. No inhibition by this toxic dose was observed in the viral protein synthesis or processing nor in the final release of the virus from the cells. However, the virions released under the influence of this 3-MC dose were found to contain mainly the uncleaved gag precursor polypeptide and a low level of reverse transcriptase. Thus, the reduced virus transmission capacity of the host cells can be ascribed to this structural defect, which presumably lowered the viral infectivity.
 ...
PMID:Tax-independent stimulation of human T-cell leukemia virus type-I expression and differential effects on its infectivity by subtoxic and toxic doses of 3-methylcholanthrene. 886 84

We have used the gibbon ape leukemia cell line MLA-144 and its corticoid-sensitive subclone MLA-E7T to analyze the mechanisms whereby interleukin-2 (IL-2) can protect T cells against dexamethasone-induced apoptosis. MLA cells are characterized by the constitutive expression of intermediate affinity receptors for IL-2, together with IL-4 receptors. MLA-144 cells secrete IL-2 and are insensitive to dexamethasone, whereas MLA-E7T cells do not constitutively produce significant amounts of IL-2 and undergo apoptotic cell death in the presence of dexamethasone. Exogenous IL-2 was shown to protect MLA-E7T cells against the apoptotic effect of dexamethasone and to increase both the DNA binding and transactivating functions of activator protein-1 (AP-1). The functional relationship between AP-1 and glucocorticoid receptors transcriptional activities was further investigated using transient expression of reporter gene constructs whose transcriptions are regulated by promoters containing TPA-responsive elements or glucocorticoid-responsive elements. The data reported here demonstrate that in MLA-144 cells, IL-2 or PMA stimulation antagonizes the glucocorticoid receptor, whereas in MLA-E7T, synergistic effects are observed between dexamethasone and IL-2 or PMA for transactivation of MMTV-CAT. Taken together with the finding that IL-2 but not PMA protects MLA-E7T from dexamethasone-induced apoptosis, our results indicate that IL-2 does not induce such a protection by repressing the transcriptional activity of the glucocorticoid receptor.
 ...
PMID:Mechanisms in interleukin-2 protection against glucocorticoid-induced apoptosis: regulation of AP-1 and glucocorticoid receptor transcriptional activities. 887 31

The three interferon-alpha2 (IFN-alpha2) sequences identified to date differ from each other in just two nucleotide positions, both of which result in changes in amino acids. Thus, the mature IFN-alpha2a protein product is characterized by a lysine residue at position 23 (AAA) and a histidine at position 34 (CAA), IFN-alpha2b has an arginine at position 23 (AGA) and histidine at position 34 (CAT), and IFN-alpha2c has arginine residues at both positions 23 (AGA) and 34 (CGT). These nucleotide variations in the DNA sequence can be distinguished by selective restriction enzyme analysis. We studied the distributions of the three IFN-alpha2 variants by analyzing chromosomal DNA from 103 Japanese volunteers and 33 patients with hematologic disorders. Fragments of 238 bp and 617 bp of the IFN-alpha2 gene containing codons 23 and 34 were amplified by PCR using specific primers, and the PCR products were analyzed with specific restriction nucleases to identify the IFN-alpha2 variant sequences. Only IFN-alpha2b gene was detected in normal volunteers, and no IFN-alpha2a gene was detected in Japanese subjects. However, IFN-alpha2c was detected in 4 of 33 (12.1%) patients with leukemia.
 ...
PMID:Determination of interferon-alpha2 allele composition in the genomic DNA from healthy volunteers and leukemic patients in Japan. 908 37

The CD9 antigen, a major platelet glycoprotein, is a member of the tetraspan superfamily. We show that treatment of K562 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) which induces megakaryocytic differentiation, leads to a seven-fold increase in CD9 expression, which becomes associated with the integrin beta1, suggesting that it is functionally relevant. The upregulation of CD9 expression precedes the appearance of the megakaryocytic-specific marker GPIIb (CD41) as well as integrins beta3 (GPIIIa/CD61), alpha v (CD51) and VLA-2 (CD49b). Both GPIIb/IIIa expression and CD9 upregulation are dependent on protein kinase C (PKC) activation since they are blocked by the specific inhibitor GF109203X. Steady-state levels of CD9 and GPIIb mRNA were also measured by quantitative RT-PCR. Both messengers were detected on resting cells and were shown to accumulate during TPA treatment. However, the increase of the CD9 mRNA was detected much earlier than the increase of GPIIb mRNA (1-2 h vs 24-48 h). Using different constructs of the 5'-flanking domain of the CD9 gene cloned ahead of the CAT reporter gene, we could demonstrate that a responsive element was located in a 52 bp fragment of the promoter of the CD9 gene. Altogether, these data suggest that CD9 upregulation in the megakaryocytic lineage could occur at early stages of differentiation.
Leukemia 1997 Aug
PMID:Upregulation of CD9 expression during TPA treatment of K562 cells. 926 83

Previously we documented the transposition of an intracisternal A particle (IAP) provirus to the interleukin 3 (IL-3) locus which resulted in autocrine transformation. In the present study, the effects of different long terminal repeats (LTRs) on IL-3 gene expression and autocrine transformation were investigated. LTRs from defective IAPs, and replication competent Moloney murine leukemia virus (MoMuLV), human T cell leukemia (HTLV), and immunodeficiency (HIV) viruses, were inserted 5' of the IL-3 promoter region, and their transforming abilities determined. Addition of the lymphocyte specific (LS) IAP-LTR to the germline IL-3 (gIL3) gene, the IAP-LTR present in the previously described transposition, resulted in a modified IL-3 gene that only infrequently transformed IL-3-dependent cells. In contrast, addition of plasmacytoma (PC) IAP-LTRs to the gIL3 gene, which were isolated from IAPs expressed in plasmacytomas, resulted in modified IL-3 genes that transformed IL-3-dependent cells more readily. The MoMuLV-LTR and the TCRdelta enhancer also stimulated high levels of IL-3 expression and autocrine transformation. In contrast, the HTLV-I, HTLV-II and HIV LTRs did not induce significant IL-3 synthesis or autocrine transformation. Consistent with these results, higher levels of CAT expression were observed in cells transiently transfected with PC-IAP-LTR or a TCR enhancer compared with LS-IAP and HTLV LTRs. In summary, the rank order for the effects of different LTRs on IL-3 expression and cell transformation is: TCRdelta-enhancer approximately MoMuLV-LTR > PC-IAP-LTRs >> LS-IAP-LTR >> HTLV-LTRs approximately HIV-LTR. These results indicate that the LS-IAP-LTR is very weak at inducing IL-3 gene transcription and additional genetic mutations may be necessary for LS-IAPs to induce autocrine transformation of hematopoietic cells. In contrast, the enhancers contained in PC-IAP-LTRs and TCR enhancers may be more effective in inducing abnormal gene expression and malignant transformation.
Leukemia 1997 Oct
PMID:Differential effects of retroviral long terminal repeats on interleukin-3 gene expression and autocrine transformation. 932 93

Human T-cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL) transforms human T cells both in vivo and in vitro. However, the long latency period between infection and development of ATL, as well as the small fraction of the infected population that actually develops this disease, suggest that factors in addition to the virus are involved in its pathogenesis. Mutation of tumor suppressor gene p53 has been found in both HTLV-I-transformed T-cell lines and ATL cases at relatively low frequency. However, increasing evidence supports p53 functional impairment in HTLV-I-transformed T cells. Tax, the major transactivator of HTLV-I, is critical for the initial events involved in transformation. We have considered the possibility that p53 may regulate transcription of viral and cellular genes important for viral replication and transformation. Inactivation of p53 function might then permit constitutive expression of these viral and cellular genes. We have investigated the effects of wild-type and mutant p53 on Tax-mediated activation of the HTLV-I long terminal repeat (LTR) and the promoters of several cellular genes including the interleukin (IL)-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF ), and IL-2 receptor alpha chain gene. Jurkat, HuT78, and U937 cells were cotransfected with plasmids containing a chloramphenicol acetyltransferase (CAT ) reporter gene under viral or cellular promoter control and the Tax expression vector, in addition to vectors for a wild-type or mutant p53. Wild-type p53 is a potent repressor of viral and cellular activation by Tax. Mutations within p53 severely inhibit this downregulation. We also show that wild-type p53 suppresses transcription from the HTLV-I LTR in Jurkat-Tax, a T-cell line stably expressing Tax, and MT-2, a HTLV-I-transformed T-cell line. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein (TBP) to the TATA motif of the HTLV-I LTR. These results suggest that p53 inactivation may lead to upregulation of viral and cellular genes and may also be important for establishment of productive viral infection and development of ATL.
 ...
PMID:Repression of transcription from the human T-cell leukemia virus type I long terminal repeat and cellular gene promoters by wild-type p53. 938 10


<< Previous 1 2 3 4 5 6 7 8 9 Next >>