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)

Monoclonal and/or polyclonal antibodies were generated against the products synthesized from two portions of the ret proto-oncogene (c-ret) cDNA expressed in Escherichia coli. These antibodies were reactive in immunoblotting with 150 kd and 170 kd proteins in cell lysates from three human neuroblastoma cell lines expressing the ret proto-oncogene. When the neuroblastoma cells were treated with tunicamycin, a protein with an apparent molecular weight of 120 kd, which is consistent with that of the c-ret protein predicted from the cDNA sequence, appeared on immunoblots. These results indicated that the 150 kd and 170 kd proteins in neuroblastoma cells are produced from a single polypeptide of 120 kd by posttranslational glycosylation. Furthermore, the antibodies detected a unique 190 kd protein as well as 150 kd protein in a cell lysate from THP-1 human monocytic leukemia cell line, suggesting that glycosylated forms of the c-ret protein are different between neuroblastoma and leukemia cells.
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PMID:Identification of the ret proto-oncogene products in neuroblastoma and leukemia cells. 200 Feb 22

To establish a model of viral infection of monocytes, we examined infection of human cells and cell lines of the monocytic series with the arenavirus Pichinde virus. We demonstrate for the first time that human peripheral blood monocytes are susceptible to Pichinde virus infection, as shown by immunoprecipatation of virus-specific polypeptides from infected cells, immunofluorescence analyses, and quantitation of virus production from infected cells. The human promyelocytic leukemia cell line HL60 did not support Pichinde virus replication, even if cells were induced with the phorbol ester phorbol myristate acetate (PMA) to differentiate to monocytes. However, the human promonocytic leukemia cell line THP-1 did support Pichinde virus replication. Replication depended on exposure of the cells to PMA. We examined the nature of the effect of PMA in the induction of THP-1 cells to support Pichinde virus replication. We found that 5 min of exposure of THP-1 cells to PMA is sufficient to support virus growth and that PMA-treated THP-1 cells remain susceptible to infection up to 4 days after the initial PMA treatment. We also showed that infection of PMA-treated THP-1 cells is mediated through protein kinase C (PKC). H7, a PKC inhibitor, was able to block both PMA-induced differentiation and Pichinde virus infection of THP-1 cells. The synthetic diacylglycerol and PKC agonist, diC8, was able to stimulate THP-1 cells to support virus growth, albeit to lower levels than PMA. Dactinomycin abrogated the ability of virus to replicate and suggested a requirement for host cell transcription. The PMA effect did not appear to relate to receptor modulation. These results suggest that PMA-induced susceptibility to Pichinde virus infection occurs at a point later than the initial binding and penetration stages and that infection depends on the activation or differentiation state of the cell.
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PMID:Characterization of Pichinde virus infection of cells of the monocytic lineage. 204 Oct 83

Several new cytostatic drugs have entered clinical phase I-II studies for the treatment of leukemia: the most promising are pyrimidine analogs such as 5-aza-cytidine, 5-aza-2'-deoxycytidine, 5-aza-cytosine arabinoside, and 2',2'-difluorodeoxycytidine. Fludarabine, a fluorinated purine analog, appears to be active in CLL and multiple myeloma. Deoxycoformycin, an adenosine analog, showed good activity in the treatment of hairy cell leukemia and T-cell neoplasias. 2-chloro-deoxyadenosine has recently been introduced into the treatment of CLL and hairy-cell leukemia refractory to deoxycoformicin. Tiazofurin, an antimetabolite which interferes with nicotine-adenine-dinucleotide (NAD) metabolism, has been applied in CML blast crisis. Other agents include 13-cis retinoic acid and 1, 25-dihydroxy vitamin D3 as differentiation inducers, and homoharringtonine, an alkylating agent which is widely used for ANLL treatment in China. Among new anthracyclines, aclarubicin, idarubicin, THP-adriamycin and fluoro-adriamycin should be mentioned. Mitoxantrone, a substituted anthraquinone, has successfully been applied in the treatment of relapsed and refractory ANLL. Amsacrine (m-AMSA), finally, is a synthetic aminoacridine which intercalates into DNA and inhibits DNA topoisomerase II. m-AMSA is not cross-resistant to anthracyclines and has been particularly active in ANLL treatment. Studies using m-AMSA alone or in combination revealed comparable results to anthracycline--containing regimens. Cardiotoxicity of the anthracycline congestive type has not been observed with m-AMSA. The EORTC Leukemia Cooperative Group has successfully used m-AMSA in several trials prepositioning this drug stepwise: from relapsed and refractory ANLL, into intensive maintenance treatment during first remission in ANLL, and, still on-going, into intensive consolidation.
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PMID:New drugs in the treatment of acute and chronic leukemia with some emphasis on m-AMSA. 206 23

Effects of transforming growth factor-beta 1 (TGF-beta 1), either alone or in combination with TNF, on the induction of differentiation of human myelogenous leukemic cell lines were examined. TGF-beta 1 alone induced differentiation of a human monocytic leukemia U-937 line into the cells with macrophage characteristics. When combined with TNF, TGF-beta 1 synergistically or additively induced differentiation associated properties. A human myeloblastic leukemia cell line, ML-1, differently responded to TGF-beta 1 in induction of differentiation. FcR activity and phagocytic activity induced by TNF were suppressed by TGF-beta 1. However, nitroblue tetrazolium reducing activity was synergistically induced by combinations of TGF-beta 1 and TNF. Scatchard analysis of TNF receptors indicated that the number of binding sites and dissociation constant of TNF for its receptors on U-937 or ML-1 cells were not changed by treatment with TGF-beta 1. Although IFN-gamma, IL-6, granulocyte CSF, and granulocyte-macrophage CSF-induced nitroblue tetrazolium reducing activity of U-937 cells, only IFN-gamma, and TNF induced it synergistically in combination with TGF-beta 1. Synergism between TGF-beta 1 and TNF was also observed in inhibition of growth of U-937 and ML-1 cells. Although TGF-beta 1 induction of differentiation of other monocytoid leukemic THP-1 cells was similar to that of U-937 cells, TGF-beta 1 only slightly induced differentiation of promyelocytic leukemic HL-60 cells, either alone or in combination with TNF. Our observations indicate that TGF-beta 1 strongly modulates differentiation and proliferation of human myelogenous leukemia cells, macrophage precursors.
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PMID:Effects of combinations of transforming growth factor-beta 1 and tumor necrosis factor on induction of differentiation of human myelogenous leukemic cell lines. 210 94

Unactivated human blood monocytes and monocytic THP-1 cells were found to respond to some leukemia cells by tumor necrosis factor (TNF) production. The TNF production by THP-1 cells in response to K562 cells was preceded by a rapid rise in [Ca2+]i, initiated within 1 h and terminated within 4 h as a refractory state took over. Neither the amount nor the duration of TNF production was enhanced by gamma-interferon. The P32/ISH cells did not induce a significant [Ca2+]i change of TNF production, while MOLT-4 cells failed to induce TNF despite their capacity to mobilize Ca2+ in THP-1 cells. The failure of P32/ISH or MOLT-4 to induce TNF was attributed primarily to a lack of stimulatory membrane molecules rather than to suppression by an inhibitory component, since liposomes carrying membrane components of K562 and MOLT-4 or P32/ISH in varying proportions elicited TNF production that precisely reflected the K562 proportion. The ability of K562 to induce TNF was selectively impaired by trypsin, whereas the ability to mobilize [Ca2+]i was more sensitive to glutaraldehyde, although once the latter activity was extinguished, the K562 cell could no longer induce TNF. These results suggest that some leukemia cells are equipped with two or more signaling membrane moieties which together stimulate monocytes for transient tumoricidal expression in the preimmune stage.
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PMID:Lymphokine-independent, leukemia cell-mediated induction of tumor necrosis factor in human monocytes. 210 56

The role of interleukin-1 (IL-1) was studied in the proliferation of promyelocytic HL-60 leukemia cells. When HL-60 cells were cultured in 10% fetal calf serum (FCS) containing medium IL-1 did not have any effect on the proliferation. In 1% FCS containing medium, the proliferation of HL-60 cells gradually decreased, but IL-1 was found to be clearly mitogenic for these cells. IL-1 did not function as an autocrine growth factor for HL-60 cells, since anti-IL-1 antibodies did not suppress the basal proliferation of these cells. IL-1 was also mitogenic for U937 but not for THP-1 cells. The suppression of HL-60 proliferation was found to be accompanied with monocytic differentiation as assessed by an increase in HLA-DR, CD11b and CD14 antigen expression. IL-1 could suppress this differentiation. HL-60 cells cultured in 1% FCS were found to express increased amounts of IL-1 receptors on the cell surface.
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PMID:Growth inhibition caused by serum depletion induces differentiation, interleukin 1 receptor expression and interleukin 1 responsiveness in the HL-60 promyelocytic leukemia cell line. 214 Jun 79

A protein complex (PC) composed of the MRP8 and MRP14 proteins has previously been shown to be a specific inhibitor of casein kinase I and II. This PC is expressed during the late stages of terminal differentiation induced in human promyelocytic HL-60 leukemia cells by 1 alpha,25-dihydroxyvitamin D3 and in human monocytic THP-1 leukemia cells by phorbol 12-myristate 13-acetate. This expression is associated with terminal cell differentiation because incubation of HL-60 cells with an agent or condition that causes suppression of growth but not induction of differentiation does not result in expression of the PC. At concentrations of 5-15 nM, the purified PC inhibited the growth of HL-60 cells and THP-1 cells, as well as other cell types belonging to different cell lineages. This growth inhibition was preceded by a reduction in [32P]phosphate incorporation and, at the higher PC concentrations, was associated with a reduction in [3H]thymidine, [3H]uridine, and [32S]methionine incorporation. The specific expression pattern and growth-inhibitory character of the PC suggests that the complex may have a role in suppressing cell growth during monomyelocytic terminal differentiation induced by specific chemical stimuli and during physiological and pathological events associated with monomyelocytic cell functions.
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PMID:A protein complex expressed during terminal differentiation of monomyelocytic cells is an inhibitor of cell growth. 227 76

In the present report we compare the capacity of two related cytokines, tumor necrosis factor (TNF) alpha and lymphotoxin (LT), to modulate mRNA levels of interleukin-6 (IL-6) in cells representing different stages of monocytic differentiation including the human leukemia cell lines HL 60, U 937, THP-1, MonoMac 1 and peripheral blood monocytes. We show that the capacity of TNF alpha and LT to induce IL-6 mRNA accumulation increases as monocytic differentiation proceeds with TNF alpha being more potent than LT, suggesting that alternate pathways may be used by differentiating cells to control expression of IL-6. In contrast, in monocytes which constitutively synthesize IL-6 transcripts, TNF alpha and LT treatment had opposite effects on levels of IL-6 mRNA accumulation. In these cells TNF alpha enhanced steady state levels of IL-6 transcripts due to mRNA stabilization, whereas LT shortened IL-6 mRNA half-life, most likely due to induction of a RNA destabilizer since LT-mediated downregulation of levels of IL-6 mRNA in monocytes could be prevented by inhibition of protein synthesis. Neither TNF alpha nor LT altered IL-6 mRNA accumulation by interfering with preexisting transcription factors since both TNF alpha and LT required de novo protein synthesis to exert their effects.
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PMID:Mechanisms of differential regulation of interleukin-6 mRNA accumulation by tumor necrosis factor alpha and lymphotoxin during monocytic differentiation. 968 34

After mezerein treatment of suspension cultures of the acute monocytic human leukemia cell line THP-1, cells became adherent to plastic culture surfaces, lost division potential, acquired Fc receptors, displayed phagocytic activity, and expressed increased nonspecific esterase staining. Serum-free RPMI 1640 medium conditioned by adherent THP-1 cells was examined for the presence of biological response modifiers. Preparative isoelectrofocusing of concentrated medium in the presence of various pH gradients of Ampholine ampholytes resulted in the separation of the following activities: fibroblast growth-stimulating activities in pH ranges of 4.10-4.55 and 5.30-5.45; colony-stimulating factor (CSF) for mouse bone marrow cells at pH 4.10-4.55; and a malignant cell growth inhibitor comigrating with a lymphocyte-activating factor (interleukin-1) at pH 6.70-6.95. Both CSF and the fibroblast growth stimulator isofocused at pH 4.10-4.55 coeluted following molecular-sieve chromatography through P-100. CSF-induced colonies were composed of nongranulocytic mononuclear cells. Chromatography through an ACA-54 column separated interleukin-1 from most of the growth-inhibitory activity.
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PMID:Biological response modifiers released by a mezerein-treated human monocytic leukemia cell line, THP-1. 241 79

We produced two hybridomas by fusion of mouse myeloma cells with splenocytes from a mouse immunized with the THP-1 human monocytoid leukemia cell line. Two cloned hybridoma cell lines, designated as TM2 and TM3, were obtained. They secreted antibodies against a unique cell surface antigen expressed on all normal peripheral blood monocytes, neutrophilic granulocytes, platelets, and mitogen-induced lymphoblasts, some cells from patients with immature-type lymphoid leukemias. However, the antibodies reacted neither with large numbers of peripheral blood lymphocytes nor with red cells. Cross-blocking studies showed that these monoclonal antibodies recognized the same or a nearly positioned antigen epitope. Immunoprecipitation of THP-1 cell extract with TM2 or TM3 under reducing and nonreducing conditions yielded a specific band of mol wt equal to 120,000 daltons. This determinant appeared to be involved in granulocyte chemotaxis, since neutrophilic granulocytes exposed to TM2 or TM3 showed a significant decrease in chemotaxis toward endotoxin-activated serum. These two monoclonal antibodies did not affect O2- release or luminol-dependent chemiluminescence of neutrophils. Moreover, they did not alter platelet aggregation induced by thrombin. TM2 and TM3 will provide a new reagent in defining the linkage between lymphoid and myeloid differentiation and intermyeloid development.
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PMID:A novel leukocyte differentiation antigen: two monoclonal antibodies TM2 and TM3 define a 120-kd molecule present on neutrophils, monocytes, platelets, and activated lymphoblasts. 241 19


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