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)

Mouse polyclonal antibodies have been raised against two human proteins (IEF [isoelectric focusing] 31, Mr = 50,000; IEF 46, Mr = 43,500) that have previously been shown to be present in HeLa cytoskeletons enriched in intermediate-sized filaments. Immunoprecipitation studies show that both proteins share common antigenic determinants with each other and with the putative human keratins IEF 36 and 44, also present in HeLa cytoskeletons. Indirect immunofluorescence studies showed that both antibodies revealed similar filamentous networks in various cultured epithelial cells of human origin. These included AMA (transformed amnion), HeLa (cervical carcinoma), normal amnion cells, Fl-amnion (transformed amnion), WISH-amnion (transformed amnion), Chang liver (liver), and Detroid-98 (sternal marrow). Human cells that did not react with both antibodies included skin fibroblasts, lung fibroblasts (WI-38), SV40-transformed lung fibroblasts, Molt 4 (leukemia), lymphocytes, and monocytes. These results were in complete agreement with the presence or absence of both proteins in two-dimensional gels of the different cell types. Exposure of AMA cells to demecolcine (24 h; 10 micrograms/ml) caused the total collapse of vimentin filaments but, as seen by indirect immunofluorescence, caused only a partial redistribution of the IEF 31 and 46 filaments. These results are taken to suggest that both proteins are components of the intermediate-sized filaments of the "keratin" type. The antibodies could be clearly differentiated by staining human bladder carcinoma EJ 19 cells, as only the IEF 46 antibody stained a filamentous network in these cells The occurrence of keratins IEF 31, 36, 44, and 46 in different cultured human epithelial cells has been studied using two-dimensional gel electrophoresis.
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PMID:Proteins IEF (isoelectric focusing) 31 and IEF 46 are keratin-type components of the intermediate-sized filaments: keratins of various human cultured epithelial cells. 618 51

Alterations in the expression of proteins associated with the cytoskeletal framework during differentiation of two human myeloid leukemia cell lines were analyzed by two-dimensional gel electrophoresis of Triton-insoluble cellular framework fractions. During in vitro differentiation of HL60 (human promyelocytic leukemia line) and U937 (human monocytoid leukemia line), several new cytoskeleton-associated (CSK) proteins are induced. All of these CSK proteins are also present in freshly isolated normal granulocytes and macrophages. One of these differentiation-induced proteins comigrates with vimentin. There are several differentiation-sensitive proteins, i.e., those that are no longer synthesized upon differentiation. The changes in CSK protein synthesis during differentiation of HL60 and U937 cells do not seem to be related to drug treatment per se since exposure to conditioned medium from phytohemagglutinin-stimulated lymphocytes as well as to dimethyl sulfoxide and 12-O-tetradecanoylphorbol-13-acetate results in the production of many similar proteins. In vitro conditions that do not result in differentiation of HL60 and U937, such as cultivation in serum-free medium, do not induce the CSK proteins that we describe. A notable finding in this study is that all of the qualitative changes in the proteins synthesized during differentiation are detected in the cytoskeletal (Triton-insoluble) fraction, whereas only minor quantitative alterations are observed in the Triton-insoluble extract. The changes in CSK protein components occur in an orderly fashion. Vimentin, an intermediate-filament protein, is synthesized in large amounts prior to changes in cellular morphology and the induction or loss of other CSK proteins. Vimentin may play an important role in the reorganization of the cytoskeleton to support the process of differentiation. The other CSK proteins are synthesized sequentially along with the morphological and functional changes during differentiation. These model systems, therefore, present an opportunity to investigate the role of specific cytoskeletal components in cellular differentiation.
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PMID:Induction of cytoskeleton-associated proteins during differentiation of human myeloid leukemic cell lines. 629 47

Mouse fibroblasts chronically infected with Moloney murine leukemia virus (MuLV) were fixed using variable amounts of formaldehyde, then examined by indirect immunofluorescence light microscopy. Several antisera were employed to detect both external and internal antigens associated with the cells, eg, MuLV gp70, tubulin, vimentin, and actin. Our results indicate that the cell membranes could be partially permeabilized to IgG molecules directed against the three cytoskeletal antigens only after 3.7%, but not 1%, formaldehyde treatment. Complete permeabilization was achieved by subsequent acetone treatment of cells after 3.7% formaldehyde fixation. In such cells, normal-appearing cytoskeletal networks of microtubules and intermediate filaments were observed. Stress fibers were also seen; however, they appeared less numerous and thinner than those of uninfected mouse fibroblasts. Further, a significant amounts of F-actin fluorescence was localized in granules in the cytoplasm of infected cells. Similar observations were made using JLS-V9 mouse cells chronically infected with 334C virus, another MuLV. These results taken together suggest that subtle differences exist in the organization of actin within MuLV-infected and uninfected mouse fibroblasts.
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PMID:The cytoskeleton of murine leukemia virus (MuLV)-infected mouse fibroblasts as observed under varying conditions of formaldehyde fixation. 631 3

The action of two structurally related DNA intercalating agents has been studied and compared, namely 4'-(9-acridinylamino) methanesulphon-m-anisidide (amsacrine, mAMSA) and 1,4-bis(butylamino)benzo[g]phthalazine (ABP) on the cell cycle and differentiation of U-937 human promonocytic leukemia cells. mAMSA (0.1 microM) and ABP (4 microM) reduced the proliferation activity to a similar extent and caused little cell mortality. At these subcytotoxic concentrations mAMSA induced the cells to accumulate at the G2 phase of the cycle, while cycle inhibition provoked by ABP was not phase specific. In addition, mAMSA caused an increase in the cell mass while ABP provoked cell shrinkage. This was consistent with the fact that ABP considerably inhibited protein synthesis, while mAMSA did not significantly affect this activity. SDS/K+DNA precipitation assays indicated that mAMSA, but not ABP, stimulated protein-DNA covalent complex formation. Finally, it was found that mAMSA, but not ABP, elicited the expression of differentiation markers, namely nitroblue tetrazolium reduction, activation of vimentin and leukocyte integrin (CD11b/CD18 and CD11c/CD18) expression, and downregulation of c-myc expression. The DNA intercalators doxorubicin and mitoxantrone, which like mAMSA induced the cells to accumulate at the G2 phase and increased the cell mass, induced the expression of differentiation markers. In contrast, the intercalators aclarubicin and caffeine and the non-intercalator novobiocin, which produced minor alterations on cell-cycle distribution and caused cell shrinkage, did not significantly elicit differentiation. These results support the conclusion that differentiation of myeloid leukemia cells by cytostatic drugs depends on the perturbations of the cell cycle, leading to disproportionate increases in cell mass.
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PMID:The action of the DNA intercalating agents 4'-(9-acridinylamino) methanesulphon-m-anisidide and 1,4-bis(butylamino) benzo[g]phthalazine in U-937 human promonocytic cells: relationship between cell cycle and differentiation. 751 13

The alpha 2-macroglobulin membrane-associated receptor (alpha 2MR) has been previously detected on hepatocytes, fibroblasts, macrophages, syncytiotrophoblasts and recently on human malignant blood cells of myelomonocytic leukemia. In cells growing in vitro from human germ cell tumors alpha 2MR mRNA was detected by Northern blotting. Endocytosis of alpha 2M from culture medium was detected in these cells by indirect immunofluorescence. In cell extracts alpha 2M and its degradation products were detected by immunoblotting. The cells expressing alpha 2MR and internalizing alpha 2M were identified as fibroblasts both by their morphology and expression of vimentin intermediate filaments. The role and function of alpha 2MR receptor in the analyzed neoplastic cells of teratomatous origin is discussed.
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PMID:Expression of the alpha 2-macroglobulin receptor on human neoplastic fibroblastoid cells. 754 57

It is well known that some of the widely used antibodies directed against hemopoietic antigens exhibit cross-reactivity with normal and neoplastic nonhemopoietic cells. By contrast, relatively little is known about the immunoreactivity of hemopoietic cells with antibodies that detect nonhemopoietic antigens. In this study 43 routinely processed bone marrow biopsy specimens containing infiltrates of acute leukemia of different subtypes were stained with a panel of 20 antibodies that detect nonhemopoietic antigens in formalin-fixed and paraffin-embedded tissue. Thirteen of the antibodies applied (KL1; BMA 120; and antibodies against epithelial membrane antigen, alpha-fetoprotein, prostate-specific acid phosphatase, prostate-specific epithelial antigen, placental alkaline phosphatase, alpha-amylase, serotonin, bombesin, beta-human chorionic gonadotrophin, desmin, and S-100 protein) did not stain blast cells in any of the cases. However, anti-vimentin, HMB45, and anti-myoglobin stained blast cells in the majority of the cases; the antibodies against thyroglobulin, actin, and carcinoembryonic antigen stained blast cells in 10% to 25% of the cases; and anti-neuron-specific enolase stained blast cells in less than 10% of the cases. No correlation was found between the leukemia subtype and the pattern of immunoreactivity. The staining specificity, (i.e., the specificity of binding of the primary antibody--immunologic vs. nonimmunologic binding), was tested by increasing the dilution of the primary antibody and comparing the staining intensity in the bone marrow specimens and control tissue. Staining specificity was confirmed only for staining with the antibodies against neuron-specific enolase and vimentin. The findings show that immunoreactivity of tumor cells in bone marrow biopsy specimens for nonhemopoietic antigens does not exclude a diagnosis of acute leukemia.
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PMID:Nonspecific immunostaining of blast cells of acute leukemia by antibodies against nonhemopoietic antigens. 762 98

Two anti-nerve growth factor receptor (LNGFR or p75NGFR) antibodies, Me20.4 and Me8211, label stromal cells with dendritic features in fresh smears and in formalin-fixed, paraffin-embedded human bone marrow (BM). The LNGFR+ cells have an oval nucleus, a scanty cytoplasm with long dendrites that intermingle with the hematopoietic cells, line the abluminal side of sinus endothelial cells, and provide the scaffold for the hematopoietic marrow. At the electron microscopy level, the immunogold tag labels the body and the long branching dendrites of fibroblast-like cells with scanty cytoplasm containing mitochondria, endoplasmic reticulum, and dense bodies. The LNGFR+ cells are positive for alkaline phosphatase, reticulin, collagen III, vimentin, TE-7, and CD13 but negative for endothelial (vWF, CD34, Pal-E), neural (CD56, neurofilament) and leukocyte markers (CD45, CD68). The LNGFR+ stromal cells appear in the fetal BM before the hematopoietic activity begins, originate from the vessel adventitia, and radiate in the Bm cavity. Long-term BM culture (LTBMC) in vitro contain LNGFR+ stromal cells. We document the presence of RNA message for the low- (LNGFR) and the high-affinity NGF receptor (NTRK1) by using RT-PCR on fresh BM aspirate and on LTBMC. BM biopsies from patients with hematologic fibrogenic diseases and in cytokine-treated cancer patients are evaluated for LNGFR+ cells: the amount of stained cells is correlated with the traditional reticulin stain in cases of myelofibrosis, therapy-related myelodysplasia, leukemia, and detected an increase of stromal cells in cytokine-treated patients. The anti-LNGFR antibodies represent a specific membrane marker for the adventitial reticular cells (ARC) of the human marrow and allow precise evaluation and quantitation of this important BM microenvironment component in vivo and in vitro.
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PMID:Bone marrow stroma in humans: anti-nerve growth factor receptor antibodies selectively stain reticular cells in vivo and in vitro. 768 1

Intermediate filaments (IF) represent major components of the cytoskeletal network. These proteins which are differentially expressed according to the cell type, constitute a dynamic structure which not only contributes to the cell architecture but also defines its state of differentiation. Furthermore, numerous observations have shown that the IF network is altered in cells transformed by tumorigenic viruses. We have previously demonstrated that HTLV-I (human T-cell leukemia virus type I) transformed T cells were characterized by a high level of vimentin transcripts and that the HTLV-I Tax regulatory protein was able to transactivate the vimentin promoter transfected into Jurkat and HeLa cells. To enlarge the scope of this study, we investigated the effects of the Tax protein on the expression and organization of IF of epithelial cells in which the IF network is composed of vimentin and cytokeratin. To this aim, we have developed a model of epithelial cells (HeLa) stably expressing the tax sequences which were introduced by using retrovirus-mediated gene transfer. Half of the Tax expressing HeLa clones were loosely adherent to the culture surface and were displaying remarkable morphological alterations, as ascertained by the presence of round-shaped or spindle-shaped cells. In these cells, expression of this viral protein correlated to a pronounced disruption in the distribution of both the vimentin and the cytokeratin networks, as shown by immunofluorescence and ultrastructural analysis. Indeed, vimentin filaments appeared to be concentrated in discrete spots throughout the cytoplasm, while the cytokeratin filaments appeared to form a dense ring around the nucleus. More importantly, mRNA and protein analysis indicate an enhanced expression of the cytokeratin 7 gene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Organization and expression of intermediate filaments in epithelial cells expressing the HTLV-I Tax protein. 769 74

Cryptophycin is a cytotoxic dioxadiazacyclohexadecenetetrone isolated from cyanobacteria of the genus Nostoc. Incubation of L1210 leukemia cells with cryptophycin resulted in dose-dependent inhibition of cell proliferation in parallel with increases in the percentage of cells in mitosis (half-maximal effects at < 10 pM). Indirect immunofluorescence studies demonstrated that treatment of A-10 vascular smooth muscle cells with cryptophycin results in marked depletion of cellular microtubules and reorganization of vimentin intermediate filaments, similar to the effects of vinblastine. Cytochalasin B caused the depolymerization of microfilaments in these cells, while neither vinblastine nor cryptophycin affected this cytoskeletal component. Pretreatment of cells with taxol prevented microtubule depolymerization in response to either vinblastine or cryptophycin. While microtubule depolymerization in response to vinblastine was rapidly reversed by removal of the drug, cells treated with cryptophycin remained microtubule depleted for at least 24 h after removal of the compound. Combinational treatments with vinblastine and cryptophycin resulted in additive cytotoxicity. Ovarian carcinoma and breast carcinoma cells which are multiply drug resistant due to overexpression of P-glycoprotein are markedly less resistant to cryptophycin than they are to vinblastine, colchicine, and taxol. Therefore, cryptophycin is a new antimicrotubule compound which appears to be a poorer substrate for P-glycoprotein than are the Vinca alkaloids. This property may confer an advantage to cryptophycin in the chemotherapy of drug-resistant tumors.
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PMID:Cryptophycin: a new antimicrotubule agent active against drug-resistant cells. 791 8

A case of epithelial mesothelioma presenting as an axillary metastasis of unknown origin with anemone cells in a 33-year-old patient with pleural effusion is reported. The differential diagnosis included tumors that can be composed of cells with anemone shape (malignant lymphoma, leukemia, malignant melanoma, carcinoma, and mesothelioma). Tumor cells in the present case were positive for cytokeratins (Cam 5.2 and AE1/3) as well as vimentin antibodies and were consistently negative for carcinoembryonic antigen, Leu-M1, leukocyte common antigen, pan-B-cell and pan-T-cell antigen, Ber-H2, S-100 protein, HMB-45, and epithelial membrane antigen antibodies. On electron microscopy, the most remarkable features were the presence of abundant, long, slender microvilli, the lack of well-developed intercellular junctions, and only occasional tight junctions in some of the tumor cells. A pleural needle biopsy confirmed the pleural origin of the proliferation. The patient refused treatment and died 3 years after diagnosis.
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PMID:Pleural mesothelioma presenting as an axillary lymph node metastasis with anemone cell appearance. 819 42


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