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)

The diagnosis of acute undifferentiated leukaemia (AUL) is made when the cells of patients with acute leukaemias cannot be classified as myeloid or lymphoid by means of morphological, cytochemical and immunological criteria. The mononuclear cells of eight different AUL patients were cultured in suspension for 3 d with or without TPA. After culture, especially in the presence of TPA, the cells of all patients expressed at least one myeloid membrane antigen. It was shown that this antigen expression was dependent on de novo protein synthesis and not influenced by inhibition of proliferation.
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PMID:In-vitro differentiation of cells of patients with acute undifferentiated leukaemia. 281 50

Two-color FACS analysis was used to study activated and "functional" T and natural killer (NK) cell subsets of circulating lymphocytes in 23 patients with B-type chronic lymphocytic leukemia (B-CLL) and in 30 healthy subjects. As compared with controls, B-CLL patients had increased absolute numbers of phenotypically activated, HLA-DR+ CD4+ and CD8+ cells and T suppressor/effector (CD11b+CD8+) cells. When patients in Rai stages II through IV (n = 11) were compared with cases in Rai stages O through I (n = 12), the former group of patients had higher numbers of activated CD4+ and CD8+ T cells and decreased levels of suppressor/effector T cells. The absolute numbers of T suppressor/inducer (CD45R+CD4+) cells were elevated in patients with stage O through I disease but within normal range in stage II through IV leukemia. We further showed that the absolute numbers of NK-like (CD16+) cells and their activated counterparts (DR+CD16+) are elevated in B-CLL patients as compared with healthy subjects. The comparison of relative T and NK subsets in the blood of patients and controls showed that the proportions of CD4+, CD8+, and CD16+ cells expressing the activation marker HLA-DR were increased in B-CLL. Furthermore, the percentage of T-suppressor/inducer (CD45R+) cells within the CD4+ population was decreased in the patients. The proportion of T-suppressor/effector (CD11b+) cells within the CD8+ subset was reduced in subjects with stage II-IV disease only. When stimulated in vitro with the T-cell-dependent inducer TPA, B-CLL cells from patients in Rai stages II through IV secreted larger amounts of IgM as compared with cells from stage O through I patients. A positive correlation was observed between the degree of phenotypic activation of CD4+ T-helper cells and their functional capacity to augment IgM secretion by autologous B-CLL cells. Our findings indicate a tumor cell-directed regulatory role of T cells (and possibly NK cells as well) in B-CLL. Furthermore, monitoring of phenotypically activated and functional T-cell subsets may be helpful in the prediction of disease progression and timing of therapy in B-CLL.
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PMID:T-cell activation and subset patterns are altered in B-CLL and correlate with the stage of the disease. 278 79

The effect of LD Ara-C (10(-8) mol/l) (Ara-C), TPA (1.6 x 10(-7) mol/l) and 13-cis-retinoic acid (RA) (10(-6) mol/l) on the differentiation in liquid culture of bone marrow cells from 5 patients with acute lymphoblastic, 17 patients with acute myelogenous leukemia, 1 patient in myeloid and 1 in lymphoid crisis of chronic granulocytic leukemia was studied. Ara-C induced morphological and cytochemical differentiation into monocytic cells in 2 cases (M1, M5 type). TPA induced convincing morphological and cytochemical features of maturation into monocytic cells in 4 cases (two M1, one M2, and one M5 type) and into differentiated myeloid cells in 2 cases (M1, M4 type). RA in one case (M2 type) out of three AML studied induced cytochemical and immunocytochemical features of maturation. The results of the study indicate that although TPA is a better inducer of blast cell differentiation than Ara-C, however, neither is a potent differentiation agent of leukemic blasts in liquid culture. The heterogeneity of leukemic blasts within the same type of leukemia was confirmed by their different response to differentiating agents.
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PMID:Study of differentiation of fresh human leukemic cells by low dose cytosine arabinoside (LD Ara-C) and 12-O-tetradecanoylphorbol-13-acetate (TPA). 281 52

The expression of three EBV open reading frames (ORF's), BBRF3, BILF1 and BMRF2 in Epstein-Barr virus (EBV)-transformed B lymphocytes from ataxia-telangiectasia (A-T) homozygotes, was studied. A-T is a human recessive genetic disorder which predisposes homozygotes and heterozygotes to cancer. Computer analysis (Robson-Garnier) was used to study the secondary structure of EBV ORF's. Three ORF's (BBRF3, BILF1 and BMRF2) found by the Kyte and Doolittle computer method to have multiple hydrophobic domains in the putative polypeptides were selected, and the polypeptides were selected, and the respective cloned EBV DNA fragments were used as probes to detect mRNA in the normal and L-6 A-T lines that was not present in the L-15 A-T line. The probe for BILF1 detected two mRNA species (3.7 and 2.0 kb) in the normal lymphoblastoid and A-T L-6 lines, while only the 3.7 kb mRNA was expressed in the A-T L-15 lymphoblasts. The probe for BMRF2 detected two mRNA species (3.7 and 2.1 kb) in the EBV-transformed normal lymphoblasts and in one A-T line (L6). The BMRF2 mRNAs were not detected in the other A-T line (L-15). This study indicated that regulation of the three EBV genes in two EBV-transformed A-T lymphoblastoid lines, differs from that in the EBV-transformed normal lymphoblastoid line. In the A-T line L-6, the three EBV genes were expressed as in EBV-transformed lymphoblastoid cells originating from a normal donor (L-21) and in the P3HR1 Burkitt's lymphoma cell line. The A-T line L-15 differed from L-6 and the other cell lines in that it expressed only one (3.7 kb) RNA species from BILF1 ORF, while ORFs BBRF3 and BMRF2 were not expressed. Since A-T L-15 line contains EBV DNA genomes, and EBV VCA is not present in these cells prior to or after TPA treatment, it is suggested that EBV gene expression is regulated by these A-T lymphoblastoid cells in a manner different from that which operates in other EBV transformed cell lines.
Leukemia 1988 Dec
PMID:Differential expression of Epstein-Barr virus (EBV) genes BBRF3, BILF1, and BMRF2 in EBV-transformed lymphoblastoid lines from ataxia-telangiectasia patients. 284 95

Activation of T cells by an antigen, a mitogen, or a combination of a phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA]) and a calcium ionophore (A23187) leads to induction of a set of lymphokine genes. Treatment of human T-cell leukemia line Jurkat by a mitogen or p40x, a transactivator protein encoded by human T-cell leukemia virus type I, activates many transfected lymphokine genes in a transient transfection assay. To study the mechanism of lymphokine gene induction, we examined the effects of mitogen stimulation and p40x on the gene for the mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) in Jurkat cells. Deletion and mutation analyses showed that the 5'-flanking region of the gene for the GM-CSF is composed of two types of regulatory elements. One sequence, located at positions -95 to -73, determines response to stimulation by either TPA-A23187 or p40x. This region contains conserved lymphokine element 2, which appears in the gene for interleukin 3 (IL-3) and is followed by a GC-rich stretch. This GC-rich stretch alone specifies inducible response to p40x but not to TPA-A23187. Another sequence, located at positions -113 to -96 upstream of a TATA-like sequence, mediates inducible response to p40x but not to TPA-A23187. This sequence includes conserved lymphokine element 1, which appears in several lymphokine-cytokine genes, such as those for IL-3, G-CSF, and IL-2. We previously showed that the simian virus 40 early region promoter was also induced by a mitogen or p40x in Jurkat cells. Deletion analysis showed that the minimum region require for stimulation by both signals are identical. These results, which indicate that p40(x) stimulates transcription of the gene for the GM-CSF or the simian virus 40 early region promoter through the same DNA element or an overlapping DNA element required for induction by a mitogen, lend further support to the notion that p40(x) can exert its function by activating a component(s) of the T-cell signal transduction pathway which is activated by an antigen or a mitogen.
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PMID:T-cell activation signals and human T-cell leukemia virus type I-encoded p40x protein activate the mouse granulocyte-macrophage colony-stimulating factor gene through a common DNA element. 285 2

The transforming protein of the Abelson murine leukaemia virus encodes a protein-tyrosine kinase. Previously, we have shown that in Abelson-transformed cells, the Abelson kinase regulates the phosphoserine content of ribosomal protein S6. Phorbol 12-myristate 13-acetate (TPA), which activates protein kinase C, induces the phosphorylation of S6 at the same five phosphopeptides as found in S6 isolated from Abelson-transformed cells. We have investigated three models whereby the Abelson kinase might regulate S6 phosphorylation via the activation of protein kinase C. First, the Abelson kinase could phosphorylate protein kinase C on tyrosine. However, we do not detect significant amounts of phosphotyrosine in protein kinase C in vivo. Second, it has been suggested that protein-tyrosine kinases might phosphorylate phosphatidylinositol. This could increase the intracellular levels of diacylglycerol and thereby activate protein kinase C. Our data strongly suggest that direct phosphorylation of phosphatidylinositol by the Abelson protein-tyrosine kinase has no physiological role. Third, an indirect activation of protein kinase C may occur via an increase in the rate of phosphoinositide breakdown. We have found that phosphoinositide breakdown appears to be constitutively activated in Abelson-transformed cells. The implications of these observations are discussed with regard to S6 phosphorylation and the mechanism of Abelson-induced transformation.
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PMID:Phosphatidylinositol turnover and transformation of cells by Abelson murine leukaemia virus. 300 37

Exposure of C57BL/6 mouse EL-4 T-cell leukemia cells to phorbol ester (12-O-tetradecanoylphorbol-13-acetate) (TPA) induced the synthesis of protein products encoded by the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) region. Analysis of TPA-treated EL-4 cells with antiserum raised against a synthetic peptide predicted by the MMTV LTR open reading frame sequence detected a polypeptide migrating in gels with an apparent molecular weight of 37,000 Mr, as well as three less prominent proteins with apparent molecular weights of 31,000, 34,000, and 39,000. Tryptic peptide analysis established the identity of the immunoprecipitated cellular proteins with the LTR proteins obtained from in vitro translation of MMTV genomic RNA. All four proteins were glycosylated and were derived from one initial nonglycosylated translation product of 21,000 Mr. The 21,000-Mr apoprotein could be detected after digestion with endoglycosidase F or pretreatment of cells with tunicamycin. Untreated EL-4 cells synthesized three species of MMTV mRNA: 35S, 24S, and 20S. TPA treatment resulted in an increased level of transcription of the three mRNAs and the appearance of a new 1-kilobase mRNA. At least 10 acquired MMTV proviruses are present in the EL-4 genome, and examination of the degree of proviral methylation revealed extensive demethylation. However, no qualitative differences in the state of proviral methylation were apparent between TPA-treated and untreated cells.
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PMID:Expression of the protein product of the mouse mammary tumor virus long terminal repeat gene in phorbol ester-treated mouse T-cell-leukemia cells. 300 59

Accumulation of cAMP in the human T-cell leukemia cell line Jurkat was stimulated by the adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) and by prostaglandin E2 (PGE2). Addition of two phorbol esters, PDiBu and TPA, markedly enhanced the NECA-stimulated accumulation of cAMP whereas the PGE2-stimulated cAMP accumulation was substantially reduced. The non-tumor-promoting phorbol ester, 4 alpha-PDD, had no effect on either NECA- or PGE2-stimulated cAMP accumulation. The ability of PDiBu to inhibit the effect of PGE2 and to stimulate the effect of NECA remained in the presence a low concentration of forskolin (0.3 microM), which per se increased both NECA- and PGE2-stimulated cAMP accumulation. Our results suggest that the effect of PK-C-activating drugs on receptor-mediated cAMP accumulation is entirely dependent on which receptor is being stimulated.
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PMID:Activation of protein kinase C inhibits prostaglandin- and potentiates adenosine receptor-stimulated accumulation of cyclic AMP in a human T-cell leukemia line. 303 16

Proliferation and differentiation of B lymphocytes is influenced by a variety of soluble mediators. The recent cloning of various cytokines has made it possible to study the effect of molecularly defined lymphokines and other cytokines on B-cell activation. In the present study, we have analyzed the effect of several cytokines on the in vitro proliferation of highly purified leukemic B cells from patients with chronic lymphocytic leukemia (CLL). The recombinant human cytokines tested included interleukins 1, 2, 3, and 4 tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN alpha), all of which are known to play a role in B-cell activation. B cells from 10 of 13 patients (all with white blood cell counts greater than 100,000/ul) did not respond to any of the cytokines tested. In contrast, B cells from 3 other patients responded well to IL-2 when preactivated for 24 h with phorbolester TPA and ionomycin. Moreover, preactivated B cells from 2 of these patients also proliferated in response to TNF-alpha, and some proliferation of unactivated B cells in response to TNF-alpha was seen in one case. Together, these results stress the clonal heterogeneity of CLL B-cell populations, and demonstrate that both IL-2 and TNF-alpha may act as a B-cell growth factor on B cells from certain CLL patients.
Leukemia 1988 Dec
PMID:B cell maturation in chronic lymphocytic leukemia. III. Effect of recombinant cytokines on leukemic B cell proliferation. 305 76

The c-fos gene is rapidly and transiently expressed when human U-937 and HL-60 leukemia cells are induced to differentiate to macrophages. We show that the expression of c-fos is controlled primarily at the transcriptional level. c-fos mRNA is very labile, with a half-life of less than 30 min. Superinduction of c-fos in the presence of cycloheximide occurs primarily because of stabilization of c-fos mRNA. When U-937 cells are serum-stimulated or treated with diacylglycerol, a c-kinase agonist, c-fos is transiently expressed to high levels; however, the cells fail to differentiate to macrophages. Furthermore, HL-60 cell variants resistant to TPA can be induced to differentiate to macrophages in the absence of detectable c-fos expression.
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PMID:c-fos expression is neither sufficient nor obligatory for differentiation of monomyelocytes to macrophages. 308 53


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