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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell surface-expressed proteoglycans mediate contacts to extracellular matrix (ECM). Human B lymphocytes produce a species of a proteochondroitin sulfate (CSPG) with an approximate molecular mass of 135-150 kDa. Using a monoclonal antibody (mAb) against B cell CSPG in flow cytometry we found that this CSPG is expressed on tumor cells of patients with CD19+ common acute lymphoblastic leukemia and on the corresponding cell lines Nalm-6, Reh and KM3. The CSPG is also present on hairy cell leukemia JOK-1 cells and weakly on the myeloma line U266. Concomitant with CSPG expression, Nalm-6 cells express the integrins alpha 5/beta 1 (CD49e/CD29) and alpha 6/beta 1 (CD49f/CD29), adhesion receptors for fibronectin and laminin, in contrast to the other two cell lines tested. Expression patterns of these adhesion receptors and CSPG were paralleled by strong adhesion of Nalm-6 to fibronectin and laminin. Adhesion of Nalm-6 to fibronectin was inhibited by the alpha 5-specific antibody SAM 1 by 80% whereas the alpha 6-specific antibody GoH3 reduced binding to laminin only by 20%. A possible involvement of surface-expressed CSPG in adhesion to ECM components was investigated by 24 h incubation of Nalm-6 cells with p-nitrophenyl-beta-D-xyloside, an inhibitor of proteoglycan glycosylation. By this treatment, both adhesion of Nalm-6 to laminin and expression of CSPG were reduced by 40-50%. Furthermore, addition of chondroitin-6-sulfate, a structural element of Nalm-6 CSPG, reduced adhesion of Nalm-6 to laminin by 60%. Chondroitin-4-sulfate, heparin and heparan sulfate did not effectively inhibit the adhesion process. These observations suggest that surface-expressed CSPG may be involved in binding of Nalm-6 cells to laminin and that the specific sulfation pattern of chondroitin-6-sulfate may be essential in this regard.
Leukemia 1996 Jun
PMID:Characterization of cell surface-expressed proteochondroitin sulfate of pre-B Nalm-6 cells and its possible role in laminin adhesion. 866 35

We have investigated the expression of the dual specific adhesion molecule, VLA-4 (CD49d/CD29) on lymphocytes obtained from 62 patients with B-CLL and compared it with normal controls, patients with other hematological malignancies, and umbilical cord blood. The mean CD49d expression in patients with CLL was lower than the other group of leukemia and the CD19+, CD5+ cells of normal peripheral blood and umbilical cord blood (P < 0.001). The patients in RAI stage 0, I and II (early stage) had even lower CD49d expression, whereas patients in RAI stage III and IV (advanced stage) had relatively higher CD49d levels. In vitro adhesion of lymphocytes to fibronectin, being the extracellular matrix ligand of CD49d, was also investigated. Lymphocytes obtained from B-CLL were found to have lower adhesion to fibronectin than that from controls (P < 0.03). Furthermore, CD49d(low) B-CLL cells had lower adhesion to fibronectin, whereas CD49d(high) B-CLL cells showed normal adhesion ratios (P < 0.002). Further phenotypic analyses revealed the presence of myeloid markers (CD13 and CD33) in most of the advanced stage patients, although these were negative in early stage cases. Expressions of CD11a and sIgM were also low but CD11b was relatively higher in the early stages of the disease. On the basis of these results, we concluded that early stages of CLL are correlated with the expression of CD49d(low), CD11a(low), CD11b(high), CD13-, CD33-, sIgM(low) and also had lower fibronectin adhesion, whereas advanced stages of CLL are associated with CD49d(high), CD11a(high), CD11b(low), CD13+, CD33+, SIgM(high) and show normal fibronectin adhesion.
Leukemia 1996 Aug
PMID:Variable expression of CD49d antigen in B cell chronic lymphocytic leukemia is related to disease stages. 870 39

The type and ability to differentiate in vitro of cells found in blastocysts of two marsupials were examined. Thirteen unilaminar blastocysts on Day 7 to Day 12 of gestation and 24 bilaminar blastocysts on Day 16 and Day 18 of gestation were collected from 11 brown antechinus, Antechinus stuartii. A total of of 77 unilaminar blastocysts on Day 5 and Day 6 of gestation and a total of 61 bilaminar blastocysts on Day 6 and Day 7 of gestation were collected from 40 stripe-faced dunnarts, Sminthopsis macroura. Pluriblast and trophoblast cells, confined to separate hemispheres, were found in unilaminar and bilaminar blastocysts, establishing that the blastocyst epithelium was not a protoderm. Hypoblast cells were found only in bilaminar blastocysts. Pluriblast and hypoblast cells did not differentiate or proliferate in up to eight weeks in culture. A small number of trophoblast cells transformed to a multinucleate state but the remainder did not proliferate or differentiate further. The presence of murine leukaemia inhibitory factor or medium conditioned by exposure to marsupial fibroblast feeder layer was not required for the maintenance of an undifferentiated state. Differentiation, proliferation and attachment of cells were not influenced by the presence of the yolk mass or the egg coats in culture. The time taken for attachment of dissociated cells varied significantly between cultures with no substrate and with collagen, fibronectin or laminin (P = 0.001, ANOVA) but did not vary significantly between substrates. The substrates did not influence the state of differentiation of the cells.
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PMID:The type and differentiation of cells in vitro from unilaminar and bilaminar blastocysts of two marsupials, Antechinus stuartii and Sminthopsis macroura. 887 95

The Mov-13 strain of mice was created by the insertion of the murine Moloney leukemia virus into the first intron of the alpha 1 (I) collagen gene. Consequently, Mov-13 embryos do not transcribe alpha 1 (I) collagen mRNA and lack type I collagen protein in the extracellular matrix (ECM). Homozygotes die within 12-14 days of embryonic development, in part from the rupture of large blood vessels, and also exhibit deficiencies in hematopoesis and assembly of the ECM (Lohler et al. [1984] Cell 38:597-607). Several matricellular proteins, proteoglycans, and growth factors bind to type I collagen, e.g., fibronectin, secreted protein acidic and rich in cysteine (SPARC), decorin, and transforming growth factor-beta. Here we investigate the expression and function of SPARC in the absence of type I collagen. We show that fibroblasts isolated from Mov-13 homozygous, heterozygous, and wild-type embryos transcribed and translated SPARC mRNA in vitro. However, accumulation of extracellular SPARC was severely affected in the tissues of Mov-13 homozygotes, whereas extracellular deposition of the secreted glycoproteins fibronectin and type III collagen was not altered. Since SPARC has been shown to be a regulator of cell shape, the functional consequences of the absence of extracellular SPARC were evaluated in collagen gel contraction assays. Fibroblasts isolated from homozygous Mov-13 mice did not contract native type I collagen gels as efficiently as fibroblasts from heterozygous littermates; however, addition of exogenous SPARC enhanced the contraction of collagen by homozygous Mov-13 fibroblasts. The stimulatory effect of SPARC was blocked by antibodies specific for the amino terminus of the protein. These results provide evidence that type I collagen is one of the major extracellular proteins that binds SPARC in vivo. Furthermore, the capacity of fibroblasts to contract ECM in vitro is enhanced by extracellular SPARC. We therefore propose that the remodeling of ECM by cells in vivo is regulated in part by a specific interaction between SPARC and type I collagen.
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PMID:Type I collagen-deficient Mov-13 mice do not retain SPARC in the extracellular matrix: implications for fibroblast function. 890 20

All trans-retinoic acid (ATRA) induces complete remission in acute-promyelocytic-leukemia (APL) patients. This study investigated the adhesive properties of APL cells for the endothelium and the extracellular matrix, their motility and the effect of ATRA on these functions. Blasts from 7 APL patients adhered to resting and IL-1-activated endothelium, to the same degree as normal PMN. Adhesion was partially mediated by ICAM-1 and, for IL-1-activated endothelium, by VCAM-1 and E-selectin. These cells showed less adhesiveness for the matrix than PMN, although they maintained the same substrate preference: they adhered to fibronectin and thrombospondin, but not to laminin and type-IV collagen. Exposure to ATRA in vitro (1 microM for 48 to 96 hr) increased the adhesiveness of APL cells; this effect was particularly evident in the case of sub-endothelial matrix and fibronectin. A similar increment in adhesiveness was observed when comparing cells from 2 patients before and after treatment with ATRA. APL cells migrated in response to fMLP and motility was increased by ATRA. In conclusion, APL cells were less adhesive to the matrix than PMN, but treatment with ATRA considerably enhanced their adhesive properties. This could be important in determining the efflux of leukemic cells from the bone marrow and their tissue infiltration during ATRA therapy.
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PMID:Effect of all trans-retinoic acid (ATRA) on the adhesive and motility properties of acute promyelocytic leukemia cells. 898 93

We have previously shown by reverse transcriptase-PCR (rtPCR) that CML CD34+ HLA-DR- cells are enriched for BCR/ABL(-) hematopoietic progenitor cells (HPC) while leukemic HPC reside predominately within CML CD34+ HLA-DR+ cells. We investigated whether the 30/35 kDa fragment of fibronectin (FN) could be used to enhance retroviral-mediated gene transfer (RMGT) in chronic phase CML marrow HPC. CML CD34+ HLA-DR- and CD34+ HLA-DR+ cells were transduced with vector supernate containing the neomycin resistance gene on plates coated with either FN or bovine serum albumin (BSA) as control, then assayed for transduced HPC in progenitor cell assays in the presence or absence of G418. Transduction efficiency of CML CD34+ HLA-DR- cells over BSA ranged from 0.09 to 7.2% (mean 3.3 +/- 1.5%), while that over FN plates ranged from 3.8 to 23% (mean 11.0 +/- 4.5%) (n = 4). Transduction efficiencies of CML CD34+ HLA-DR+ cells ranged from 0.4 to 9.8% (mean 3.7 +/- 1.7%) and 6.0 to 26% (mean 17.3 +/- 4.5%) (n = 5) over BSA and FN, respectively. rtPCR analysis for BCR/ABL mRNA of individual G418-resistant HPC generated from CD34+ HLA-DR- cells revealed that normal BCR/ABL(-) HPC were successfully transduced under these experimental conditions. These results demonstrate the feasibility of transducing normal CML primitive HPC, and illustrate the potential clinical use of FN in the setting of gene therapy for CML, as well as other diseases.
Leukemia 1997 Jan
PMID:The 30/35 kDa chymotryptic fragment of fibronectin enhances retroviral-mediated gene transfer in purified chronic myelogenous leukemia bone marrow progenitors. 900 33

The non-sedating anti-allergic drug astemizole, apart from its potential to antagonise H1 receptors, inhibits the release of inflammation mediators from mast cells. To study the mechanism of this inhibition, we investigated the effects of astemizole and one of its active metabolites, norastemizole, on different phases of Fc epsilon RI (the high affinity receptor for the immunoglobulin IgE) receptor-activated signal transduction in rat basophilic leukemia cells (RBL-2H3), leading to exocytosis. Cells were stimulated either through antigen, or thapsigargin, or synergistic combinations of Fc epsilon RI receptor activation with either adenosine A3 receptors or integrins, activated by fibronectin adherence. The effects of the drugs on mediator release, inositol 1,4,5-trisphosphate formation, tyrosine phosphorylation of cellular proteins and Ca2+ fluxes were investigated. Inositol 1,4,5-trisphosphate levels are not affected. Astemizole increased tyrosine phosphorylation in resting cells, especially a 96-kDa protein band. Particularly tyrosine phosphorylation related to post Ca2+ processes is changed after cell triggering in the presence of astemizole. Both drugs inhibit the influx of 45Ca2+, with similar dose response curves as for the inhibition of exocytosis. Astemizole but not norastemizole, when used in resting cells, released Ca2+ from intracellular stores. Astemizole (> 15 microM) also induced exocytosis in resting cells. It did not induce additional changes in its inhibiting effect when cells were triggered with synergistic combinations of Fc epsilon RI receptor activation with either adenosine A3 receptors or integrins. Effects on haemolysis of erythrocytes and differential scanning calorimetry in liposomes showed clear differences in membrane perturbation between astemizole and norastemizole. The observed differences, and the role of membrane perturbation in the action on Ca2+ fluxes, are discussed.
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PMID:Effects of the anti-allergics astemizole and norastemizole on Fc epsilon RI receptor-mediated signal transduction processes. 908 77

Rat basophilic leukemia cells will adhere to and spread out on fibronectin coated surfaces in an integrin dependent manner. Adhesion and spreading on fibronectin leads to increased degranulation, inositol phosphate production, phospholipase D activation, and increased production of prostaglandin D2 and leukotriene C4 when the cells are activated through the high affinity IgE receptor. Rat basophilic leukemia cells will also adhere to surfaces coated with anti-rat class I antibodies, poly-L-lysine, and a lectin purified from Tetragonolobus purpureas. In all cases, antigen activated cells, which were adherent, displayed increased signaling, degranulation and eicosanoid production as compared to cells which were non-adherent. Cells which adhere to either anti-rat class I antibodies or poly-L-lysine also spread even though this is not mediated through integrins. In contrast, adhesion to the lectin from Tetragonolobus did not cause any appreciable spreading unless the cells were also triggered through the IgE receptor. Cells were also able to bind to fibronectin immobilized on polystyrene beads which mimics adhesion but does not allow spreading. However, these cells exhibited no increased signaling, degranulation, or eicosanoid production. Furthermore, rat basophilic leukemia cells can be modified by incubating them in the presence of biotinylated-phosphatidylserine which becomes incorporated into the membrane. These modified cells will adhere to streptavidin coated plates while unmodified cells will not. However, these modified cells do not spread, even after activation with antigen, and they show no increased degranulation or production of eicosanoids. These results indicate that adhesion itself is not sufficient for upregulation of the cells in response to antigen and that spreading of the cells may be the critical component.
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PMID:Increased degranulation and phospholipase A2, C, and D activity in RBL cells stimulated through FcepsilonR1 is due to spreading and not simply adhesion. 909 51

Receptor tyrosine kinases (RTK) play an important role in the signal transduction of normal and malignant cells. There are different families of RTKs which are mainly characterized by differences in the ligang-binding extracellular domains. Axl (or UFO/Ark) is the first member of a new class of RTK with two fibronectin type III domains and two immunoglobulin-like domains present at the extracellular domain. The axl-gene has been isolated by means of gene transfection studies using DNA of patients with chronic myelogeneous leukemia. For a previous and the present study, we used a sensitive reverse-transcriptase polymerase chain reaction assay to detect axl's mRNA in cells from normal and malignant hematopoietic tissue. Axl's mRNA expression was mainly detected in myelo-monocytic cells, whereas much weaker transcription was seen in lymphatic cells and in lymphatic leukemias. In normal bone marrow, axl was heavily transcribed in marrow stromal cells. Further, we analysed Axl protein expression using monoclonal antibody M50 in peripheral stem cell harvests; in most harvests, no co-expression of CD34 and Axl was detected. However, in one patient with AML in complete remission, Axl was co-expressed on 80% of the CD34-positive population. These data show that axl is preferentially expressed in monocytes and stromal cells. Furthermore, a fraction of CD34-positive progenitor cells may express Axl. The exact mechanism for transformation of myeloid progenitor cells through Axl, however, remains to be determined.
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PMID:Recent progress on the role of Axl, a receptor tyrosine kinase, in malignant transformation of myeloid leukemias. 913 Jun 17

Adhesion of normal colony-forming cells (CFC) to bone marrow (BM) stroma and the extracellular matrix (ECM) component fibronectin (FN) depends at least in part on the alpha4beta1 and alpha5beta1 integrins and the CD44 receptor. Aside from anchoring progenitors in the marrow microenvironment, beta1 integrin-dependent adhesion of normal CFC is associated with inhibition of their proliferation. In contrast to normal CFC, chronic myelogenous leukemia (CML) Ph+ CFC adhere significantly less to either stroma or FN. CML Ph+ CFC proliferation is also not inhibited by coculture with stroma or FN. However, equal numbers of alpha4, alpha5, and beta1 integrins and CD44 are present on CML and normal CD34+ cells. We have previously demonstrated that beta1-dependent adhesion to and subsequent proliferation inhibition by FN can be restored when CML Ph+ CFC are incubated with the beta1 integrin activating antibody, 8A2, and demonstrated a role for the alpha5beta1 integrin in this phenomenon. Since the integrin alpha4beta1 and the proteoglycan form of CD44 may cooperate in establishing normal CFC adhesion to FN, we examined if treatment of CML Ph+ CFC with 8A2 also restores the cooperativity between beta1 integrins and CD44. We demonstrate that 8A2 induces adhesion of CML Ph+ CFC not only to intact FN but also to alpha4beta1, alpha5beta1, and proteoglycan binding fragments of FN. 8A2-induced adhesion to these fragments and peptides also results in a significant inhibition of the proliferation of CML Ph+ CFC. Addition of antibodies to either the alpha5, alpha4, or beta1 integrins, antibodies against the CD44 receptor, or removal of chondroitin sulfate glycosaminoglycans from the surface of CML CD34+ HLA-DR+ cells significantly reduced the 8A2-induced adhesion to and adhesion-mediated inhibition of proliferation by FN. These studies demonstrate that activation of beta1 integrins on CML Ph+ CFC not only results in upregulation of beta1 integrin-dependent adhesion and adhesion-mediated inhibition of proliferation, but also in the restoration of cooperation between beta1 integrins and CD44. These studies suggest that decreased beta1 integrin avidity may also affect the function of the proteoglycan adhesion receptor CD44, both of which may contribute to the abnormal circulation and expansion of malignant progenitors in CML.
Leukemia 1997 Jun
PMID:Activation of beta1 integrins on CML progenitors reveals cooperation between beta1 integrins and CD44 in the regulation of adhesion and proliferation. 917 35


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