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)

HCs have a distinctive profile of matrix-binding integrin receptors which partly reflects their activated nature. HCs show differing functional responses to individual adhesive proteins, and these are mediated by particular integrin heterodimers. In particular, HCs are motile on Vitronectin (VN), and this motility is mediated by alpha v beta 3. HCs are immobile but actively spread on Fibronectin (FN) and this response is mediated by beta 1 integrins. M-CSF enhances the mobility (chemotaxis and chemokinesis) of HCs, and this response is partly mediated by alpha v beta 3. HCs synthesise and assemble fibronectin and this is, at least partly, the cause of the distinctive bone marrow fibrosis of hairy-cell leukaemia.
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PMID:Specific tissue invasion, localisation and matrix modification in hairy-cell leukemia. 782 48

By using fresh leukemia cells from 5 cases of acute monocytic leukemia M5 as in vitro model, we investigated the effects of recombinant human transforming growth factor beta 1 (rhTGF-beta 1) on differentiation induction of fresh leukemia cells. The results indicated that after 6 days of induction with TGF-beta 1 in a concentration of 10 ng/ml, leukemia cells in 5 AML-M5 patients differentiated obviously to maturation. The proportion of monoblasts and premonocytes was reduced, while that of mature mononuclear cells elevated. Following administration of TGF-beta 1, alpha-nonspecific esterase (alpha-NSE), whose expression could be inhibited by sodium fluoride, remained positive and peroxidase (POX) was shown to be weakly positive. These results demonstrated that TGF-beta 1 may induce in vitro differentiation of fresh leukaemia cells, but the reactions to TGF-beta 1 may vary in different cases.
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PMID:[The effects of recombinant human transforming growth factor beta on inducing differentiation of fresh leukemia cells in acute monocytic leukemia M5]. 783 37

Subunit specific radioimmunoassay for aldolase isozymes were developed for the quantification of human aldolase A and B. Aldolase B immunoreactivities were predominantly high in adult normal liver, while aldolase A was distinctly low. Aldolase A was high, while aldolase B was low in neonatal liver compared with the adult liver. Aldolase A immunoreactivities were almost the same as those of aldolase B in fetal liver (28 weeks). Aldolase A was predominantly found in human hepatoma tissues, whereas aldolase B was distinctly low in the same hepatoma tissues. With regard to human hepatoma cell lines, aldolase A was also predominantly found in HepG2 and PLC/PRF/5 cell lines, whereas aldolase B levels were extremely low. Almost the same results were obtained from mRNA expression of aldolase A and B in human hepatoma cell lines by the method of northern hybridization. Effects of various reagents on differentiation of hepatoma cell lines were investigated. Neither Dimethyl Sulfoxide (DMSO) and 12-O-Tetradecanoylphorbol-13-acetate (TPA), which are known to be the inducers of differentiation of human leukemia cell lines such as HL-60, nor Transforming Growth Factor-beta 1 (TGF-beta 1) and Hepatocyte Growth Factor (HGF), which are known to be growth inhibitors, could cause the differentiation of hepatoma cell lines in the alteration of aldolase isozymes. The same data were shown in mRNA expression of aldolase isozymes. These results suggest that aldolase A immunoreactivities and mRNA expression are both predominantly high in hepatoma cell lines, and the reagents such as DMSO, TPA, TGF-beta 1 and HGF which tried to differentiate the hepatoma cell lines used in this study were not effective in the alteration of aldolase isozymes.
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PMID:[Immunoreactivities and messenger RNA expression of aldolase A and B in human hepatoma cell lines]. 786 61

Transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF) are known as protein cytokines involved in differentiation as well as in maturation processes within the hematopoietic system. Both enhance the proliferation and/or collagen synthesis in fibroblasts and are found within the alpha-granules of megakaryocytes. To learn more about the regulation mechanisms involving synthesis and secretion of these cytokines it is important to develop suitable experimental conditions. We have applied the reverse hemolytic plaque assay (RHPA) to CD61+ megakaryocytes prepared from bone marrow of hematologically normal patients. By means of the RHPA, the spontaneous and stimulated secretion of TGF-beta 1 and PDGF could be analyzed at the single cell level. According to morphometric analysis, predominantly small megakaryocytes including precursors (pro- and megakaryoblasts) secrete TGF-beta 1 and PDGF under physiological conditions. Furthermore, the proportion of actively secreting megakaryocytes increased significantly following treatment with recombinant human (rh) IL-3 for 8 h. A slight induction was also appreciated after stimulation with interleukins rhIL-1 or rhIL-11. Because IL-3 as well as IL-11 are known as efficient growth factors for human megakaryocytes in vitro, our data provide insights into the regulatory mechanisms involved in megakaryopoiesis and the development of myelofibrosis.
Leukemia 1995 Feb
PMID:Detection and quantification of transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF) release by normal human megakaryocytes. 786 69

The biosynthesis of neolacto glycosphingolipids is thought to proceed via reactions catalysed by the two enzymes beta 1-3-N-acetylglucosaminyltransferase (beta 1,3GlcNAcT) and beta 1-4 galactosyltransferase (beta 1,4GalT). In general, only the products of the latter enzyme have been isolated from tissues and structurally characterized. Among the GlcNAc beta 1-3-R glycosphingolipids, only lactotrioasylceramide (Lc3Cer, the initial product in the biosynthesis of neolacto glycosphingolipids) has been isolated and structurally characterized. Longer-chain glycosphingolipids with a terminal GlcNAc-beta 1-3-R structure are considered to be intermediates in the synthesis of complex neolacto glycosphingolipids. We have detected a series of GlcNAc beta 1-3-R glycosphingolipids in extracts obtained from human leukocytes isolated from patients with leukaemia using a monoclonal antibody (TE5) which specifically recognizes these compounds. The structures of three of these compounds purified from chronic myelocytic leukaemia (CML) cells have been determined using a combination of enzymatic, immunostaining and chemical methods. The compounds were found to have the following structures: GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer (Lc3Cer) GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer (nLc5Cer) GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer (nLc7Cer) A longer-chain compound, apparently nLc9Cer, was also detected. TLC immunostaining analysis of glycosphingolipids isolated from cells obtained from patients with various leukaemias demonstrated that GlcNAc beta 1-3-R glycosphingolipids have a distribution that depends on the stage of differentiation and lineage of the cell population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structural characterization of intermediates in the biosynthetic pathway of neolacto glycosphingolipids: differential expression in human leukaemia cells. 794 52

The expression of alpha 1,3 fucosylated type 2 antigens is generally thought to be restricted to myeloid cells among normal human haemopoietic tissue. The distribution of three fucosylated antigens [Lewis X (Le(x)), sialyl Lewis X (sLex) and VIM2] was investigated among nine human leukaemia cell lines by fluorescence activated cell sorting (FACS) analysis. As expected, all myeloid cell lines were positively stained by antibodies against these three fucosylated antigens. Unexpectedly, two T-lymphocytic cell lines (CCRF-CEM and MOLT4) were found to express Le(x) and VIM2, and the plasma, B-cell line, RPMI 8226, expressed all three fucosylated antigens. Enzymatic and RNA analyses [Northern blot and reverse transcription polymerase chain reaction (RT-PCR)] were used to evaluate possible control points in the biosynthetic pathway for Le(x) and sLex. beta 1,4 Galactosyltransferase (beta 1,4GalT, an enzyme involved in the synthesis of the core oligosaccharide of the three fucosylated antigens) activity and the corresponding mRNA were found in all of the leukaemia cell lines, regardless of whether or not they expressed the fucosylated antigens. In contrast, alpha 1,3 fucosyltransferase (GDP-fucose:beta-D-N-acetylglucosaminide 3-alpha-L-fucosyltransferase; alpha 1,3FT) activity and the corresponding mRNA were found only in those cell lines expressing fucosylated antigens. Based on RNA analysis, acceptor specificity and N-ethylmaleimide inhibition studies, it was concluded that all of the cell lines expressing fucosylated antigens contained alpha 1,3FTIV (myeloid alpha 1,3FT). This appeared to be the major alpha 1,3FT in the myeloid and T-lymphocytic cell lines. Interestingly, even though both types of cell lines expressed the same alpha 1,3FT, only the myeloid cell lines expressed sLex, whereas all of the myeloid and T-lymphocytic cell lines expressed a structural analogue of sLex (i.e. VIM2). In contrast to the myeloid and T-cell lines, RPMI 8226 cells contained more than one fucosyltransferase activity. Acceptor specificity analysis demonstrated that this cell line contains alpha 1,3 and alpha 1,4FTs. Among the fucosyltransferases expressed by RPMI 8226, alpha 1,3FTIV accounted for only a small amount of the total activity. The results of this study demonstrate that fucosylated antigens, which are generally considered to be myeloid specific antigens, are also expressed by lymphocytic leukaemia cell lines, and that the types of fucosylated antigens and fucosyltransferases expressed in these cell lines vary.
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PMID:Expression of fucosylated antigens and alpha 1,3 fucosyltransferases in human leukaemia cell lines. 794 57

The human promyelocytic leukaemia cell (HL-60) undergoes differentiation into a macrophage-like form when exposed to both tumour promoting- and non-promoting phorbol esters. We have investigated the effect of the two non-promoting phorbol esters, 12-deoxyphorbol-13-O-phenylacetate (Dopp) and 12-deoxyphorbol-13-O-phenylacetate-20-acetate (Doppa) on HL-60 cultures, and compared them with the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). All phorbol esters tested were found to be able to stop HL-60 proliferation and induce cell adherence and morphological changes characteristic of differentiation. TPA, fully differentiating at 1 nM, was more potent than Dopp and Doppa, which required 100 nM for full differentiation effects within the 4 day study. Doppa initially appeared weaker than Dopp at inhibiting incorporation of thymidine, the earliest effect studied, but we were able to detect rapid C-20 deacylation of Doppa, converting it to Dopp, using an HPLC protocol presented here. A detailed study of this thymidine incorporation inhibition showed that both TPA (10 nM or greater) and Dopp (500 nM or greater) have very similar time courses, with 50% inhibition occurring at approximately 12 h, in contrast to Doppa which had a significantly delayed time course at all doses tested. Exposure tests indicated that Dopp and Doppa could be washed from the cells much more easily than TPA. The data presented here strongly support the notion that the metabolic conversion of Doppa to Dopp by HL-60 cells was necessary to mediate its differentiating effects. Since protein kinase C (PKC)-beta 1, present in HL-60 cells, has been found to be the only PKC isotype activated so far in vitro by Doppa, our results suggest that activation of this isotype is not sufficient to drive HL-60 differentiation in vivo.
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PMID:HL-60 cell differentiation induced by phorbol- and 12-deoxyphorbol-esters. 795 99

Deletion of the short arm of chromosome 9p involving the beta 1-interferon (IFN) gene has been implicated in the process of malignant transformation in lymphomas and acute lymphoblastic leukemias. Since cytogenetic analysis is frequently unsuccessful in clinical samples, we used a recently described differential PCR technique to detect losses within the beta 1-IFN gene in 86 acute leukemias. Using differential PCR, no beta 1-IFN deletion was detected in 44 acute myeloid leukemia (AML) and eight control samples. However, five of 42 acute lymphoblastic leukemia (ALL) probes (12%) exhibited loss of the beta 1-IFN gene (three common ALL, two T-ALL). Cytogenetic analysis was performed independently in three of these five cases and revealed abnormalities of chromosome 9p in two samples. Two of five T-ALL cases exhibited a loss within the beta 1-IFN gene, compared with 3/29 c-ALLs, suggesting a predominance of IFN gene loss in T-ALLs. These data indicate that PCR can be used for rapid detection of gene dosage phenomena in clinical leukemia samples.
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PMID:Detection of allelic loss within the beta 1-interferon gene in childhood acute lymphoblastic leukemia using differential PCR. 800 58

Measurement of glycosyltransferase activity in whole cell extracts is often complicated by the fact that several enzymes in an homogenate are capable of using the same nucleotide sugar donor, thereby generating a range of products from both an exogenous and any endogenous acceptors. We report the use of a novel combination of techniques to simultaneously identify and quantify the products generated from a whole cell extract in a single experiment. Several radiolabeled glycosphingolipid products were generated by the addition of UDP-[14C]Gal to a reaction mixture containing an homogenate from a human leukemia cell line, THP-1. After the 14C-labeled products were separated on a TLC plate, storage phosphor technology and immunostaining (with carbohydrate sequence-specific monoclonal antibodies) were used sequentially on the same plate to simultaneously identify and quantify each of the glycosyltransferase products. This method allows product identification and quantification in the femtomole range. Thus, low levels of endogenous acceptors were easily detected. We have used a similar method with UDP-[3H]Gal to obtain glycosyltransferase product profiles from several human leukemia/lymphoma cell lines and subsequently identify two galactosyltransferase activities in these cell lines: UDP-Gal:Gal beta 1-4Glc beta 1-1Cer alpha 1,4galactosyltransferase; and UDP-Gal:GlcNAc beta 1--3Gal beta 1--4Glc beta 1--1Cer beta 1,4galactosyltransferase. In addition to product characterization, this method was used with reaction mixtures at different pH to demonstrate the usefulness of the method for characterizing multiple enzyme activities simultaneously.
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PMID:Analysis of glycosphingolipid glycosyltransferase products on TLC plates by combined storage phosphor and immunostaining techniques. 805 57

The integrin family of adhesion receptors includes at least 11 different alpha subunits and 6 different beta subunits which are associated to form 14 different alpha beta heterodimers, divided into three subfamilies. In particular, beta 1 subfamily integrins (VLA 1-6 proteins) have been found to mediate cell adhesion to extracellular matrix (ECM) component such as fibronectin, collagen, laminin; however, VLA-4 has been found to exhibit both cell-cell and cell-matrix adhesion functions. The reactivity of VLAs is virtually ubiquitous and independent of line or tissue specificity. However, the expression of individual VLAs within single tissues can be modulated according to the type or functional status of the cell. One of the main reasons for interest in these molecules is that they may play a determining role in neoplastic transformation and diffusion; in particular, in lymphoproliferative syndromes, a lack of cell adhesiveness or an abnormal adhesion pattern in neoplastic lymphocytes may free these cells from regulation, thus contributing towards the development of leukemia and/or lymphoma. Studies of VLA expression in B-cell leukemia/lymphomas show a modulation of VLA3 and VLA4 reactivity. The most interesting element is the identification of a VLA3/VLA4 pattern associated with B-cell chronic lymphocytic leukemia (B-CLL) characterised by a reduced expression of VLA4 and the constant expression of VLA3. Although the value of VLA3 as an additional marker for the diagnosis of classical B-CLL is indisputable, the biological/functional significance of this reactivity remains to be confirmed.
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PMID:Structure and function of VLA integrins: differential expression in B-cell leukemia/lymphoma. 816 51


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