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)

To test the feasibility of using the human epidermal growth factor receptor (EGFR) as a model for growth factor receptor action in human hematopoietic cells, we infected Burkitt lymphoma cells (Namalwa) with a recombinant amphotrophic retrovirus containing a thymidine kinase promoter-driven human EGFR complementary DNA and the neomycin resistance gene. Neomycin-resistant cells expressing surface EGFR were selected by cell sorting using anti-EGFR monoclonal antibody 225. The selected cells expressed a Mr 170,000 protein immunoprecipitated by monoclonal antibody 225 and apparently identical to EGFR from A431 carcinoma cells. Infected Namalwa cells expressed 42,000 epidermal growth factor (EGF) binding sites/cell, and Scatchard analysis showed two affinities (Kd approximately 5 nM and approximately 0.5 nM). EGFR autophosphorylation was detected using antiphosphotyrosine antibodies after 5 min exposure to EGF. EGF binding induced rapid EGFR internalization (t1/2 = 9 min) and mobilization of transferrin receptors to the cell surface within 1 min. In fetal bovine serum-containing and serum-free cultures, EGF did not stimulate Namalwa cell proliferation. However, in the presence of 1.25% dimethyl sulfoxide (DMSO), EGF caused a dose-dependent increase in DNA synthesis. DMSO induced a cell cycle block in G1, which was partially reversed by EGF. DMSO induced changes in some B-cell markers suggesting cellular differentiation and increased surface EGF receptor number. Cells grown in DMSO and EGF were established as an EGF-dependent cell line for greater than 12 weeks, whereas cells grown in DMSO without EGF died within 1-2 weeks. Namalwa cells expressing EGFR demonstrated more rapid tumor growth in athymic mice. These studies demonstrate expression of functional EGFR mediating early biochemical and growth responses in a human hematopoietic cell, and indicate that EGFR can be used as an effective model in human hematopoietic cells. Results using DMSO are consistent with studies in other human leukemia cells indicating that agents inducing differentiation can restore growth factor dependence in previously factor-independent leukemia cells.
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PMID:Expression of functional epidermal growth factor receptors in a human hematopoietic cell line. 170 31

Yam 1B, a human B lymphoblastoid cell line, spontaneously produced an immunoregulatory factor, which suppresses blastogenesis and antibody formation by human lymphocytes. The Yam 1B cells, which were derived from the peripheral blood of an adult T-cell leukemia patient, have been established and maintained in our laboratory since 1985. This cell line expressed mature B-cell surface antigens including surface immunoglobulin M (IgM), CD23, and HLA-DR; had cytoplasmic IgM; and secreted small amounts of IgM in the culture supernatants. Yam 1B was positive for Epstein-Barr virus-associated antigen (EBNA) but negative for adult T-cell-associated antigen (ATLA). The serum-free Yam 1B culture supernatants (SN) inhibited the expression of transferrin R, but neither the expression of interleukin 2 (IL-2) R(CD25) nor the production of IL-2 in the lymphocytes stimulated with phytohemagglutin. Yam 1B SN also inhibited DNA synthesis by human T and B lymphocytes and immunoglobulin generation by normal B cells as well as by Epstein-Barr virus-transformed human B lymphoblastoid cell lines. The inhibitory activity of Yam 1B SN was inactivated at 56 degrees C and at pH 10 but was relatively stable at pH 2. It was abrogated by digestion with pronase and was partially stable by digestion with trypsin. Fractions collected from a Sephacryl S-300 gel filtration column (Pharmacia Fine Chemicals, Uppsala, Sweden) were found to have a peak of inhibitory activity of cell proliferation associated with molecules of apparent MWr of 43,000 to 67,000. The inhibitory activity of Yam 1B SN was not blocked by the anti-transforming growth factor beta antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of lymphocyte blastogenesis and antibody production by soluble factor released by a human B-lymphoblastoid cell line. 179 Mar 7

We have previously demonstrated (Guan X.-P., Hromchak, R. A., and Bloch, A. (1989) Cancer Commun. 1, 111-115) that ML-1 human myeloblastic leukemia cells differentiate to monocyte/macrophage-like cells by the sequential action of competence and progression factors. Tumor necrosis factor-alpha, transforming growth factor-beta, and the phorbol ester tetradecanoylphorbol acetate were found to induce competence, whereas a 77-kDa glycoprotein (DF77) isolated from mitogen-stimulated human leukocyte-conditioned medium initiated progression. In this communication we show DF77 to be an isoform of human transferrin. Hemin or soluble iron complexes did not induce differentiation progression, suggesting that the participation of transferrin in ML-1 cell differentiation may not be related to its iron-carrying capacity.
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PMID:Identification of transferrin as a progression factor for ML-1 human myeloblastic leukemia cell differentiation. 186 25

Prealbumin, albumin, orosomucoid (including the cellular variant orosomucoid2), alpha 1-antitrypsin, haptoglobin and transferrin were quantified in 107 cell samples from acute and chronic myeloid leukaemia, seven polycytaemia, seven normal blood marrow and 56 normal blood leukocytes by crossed immunoelectrophoresis. By statistical multivariate analyses, the individual plasma proteins and their combined protein patterns were correlated with the diagnoses and it was demonstrated that acute leukaemia cell samples contained significantly different protein patterns compared with the other diagnostic groups and normal controls. By comparison with the white blood cell differential count, in 78 samples of acute leukaemia, it was demonstrated that the protein patterns were significantly correlated with the specific cell types in the samples. In all, the differential counts accounted for about 29% of the variation in protein patterns. Alpha 1-antitrypsin was found significantly correlated with the myeloblasts and myelo-band cells. Orosomucoid2 and haptoglobin were significantly correlated with mature granulocytes and albumin was significantly correlated with lymphocytes. In some cell samples, after cytotoxic treatment of acute leukaemia, the granulocytes did not have orosomucoid2 despite normal morphology, suggesting defective maturation of these granulocytes. These results indicate that the mechanisms responsible for uptake of plasma proteins are highly specific for different cell types and in the case of myeloid cells specifically related to cell differentiation.
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PMID:Correlation between leukocyte-associated plasma proteins and white cell differential count. 188 76

Colony-stimulating factor-1 (CSF-1 or M-CSF) supports the proliferation and survival of mononuclear phagocytes by binding to a receptor (CSF-1R) encoded by the c-fms proto-oncogene. Whereas the CSF-1R kinase is normally regulated by ligand, receptors bearing 'activating mutations' act constitutively as enzymes and can transform fibroblasts and haemopoietic cells of different lineages. Introduction of human CSF-1R enables mouse NIH-3T3 cells to form colonies in agar in response to human CSF-1 and to proliferate in serum-free medium supplemented with CSF-1, albumin, transferrin and insulin. Similarly, expression of human CSF-1R in interleukin 3-dependent mouse FDC-P1 myeloid cells enables them to grow in CSF-1. High levels of CSF-1R expression in FDC-P1 cells can induce factor-independent growth which is abrogated by a 'neutralizing' monoclonal antibody to the receptor. Therefore, critical mutations in the c-fms gene or overexpression of CSF-1R in immature myeloid precursors might each contribute to leukaemia.
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PMID:Signal-response coupling mediated by the transduced colony-stimulating factor-1 receptor and its oncogenic fms variants in naive cells. 215 60

The neoplastic lymphoid cells in 33 patients with chronic lymphocytic leukemia (CLL), 1 case of prolymphocytic leukemia (PLL), and 29 patients with various types of non-Hodgkin's lymphoma (NHL) were examined for the expression of transferrin receptors (TR) using a panel of three anti-TR monoclonal antibodies (MAb). Both immunofluorescence and immunoperoxidase techniques were applied in each case. All cases of B-CLL (31) were negative for TR expression, while both the cases of T-CLL, and the only case of T-PLL showed significant TR-positive cell populations. Similarly, all 13 cases of "low-grade" NHL were TR negative, while 6 of 7 cases of "high-grade" lymphomas (lymphoblastic and immunoblastic) had up to 28% TR-positive cells. A proportion (4/9) of "intermediate grade" lymphomas had 10-15% TR positivity. Interestingly, the majority of B-leukemia/lymphoma (49/55) cases were TR negative, while all 8 cases of T-cell leukemia/lymphoma were TR positive. This clearcut association of TR expression with high-risk morphologic and immunophenotypic subgroups of lymphoid leukemia/lymphoma points to the potential role of TR as a prognostic marker in lymphoproliferative disorders.
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PMID:Correlation of transferrin receptor expression with histologic grade and immunophenotype in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. 218 55

Primary and secondary colony formation of two new human myeloid leukemia cell lines (BRM and DD) were studied in serum-free semisolid cultures. The results indicate that bovine serum albumin and transferrin were essential for clonal growth in chemically defined medium. Insulin contributed only moderately beneficial effects. Initial cell density was also a major modulator of plating efficiency. Positive cooperation between the leukemia cells was shown by using autologous conditioned media. This is the first serum-free culture method that allows self-renewal of human myeloid leukemia cell lines in terms of secondary colony formation in methylcellulose cultures.
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PMID:Clonal growth and self-renewal of human myeloid leukemia cell lines (BRM and DD) in serum-free semi-solid culture. 227 80

Treatment of two human leukemia cell lines with 1.25% dimethyl sulfoxide at 37 degrees C results in a rapid increase in the number of transferrin receptors on the cell surface detected by fluorescein-labeled anti-transferrin receptor antibodies. Both HL-60 cells, a human myeloid cell line, and K562 cells, a human erythroid-myeloid cell line, showed a 25-65% increase in cell surface transferrin binding in parallel experiments. Scatchard plot analysis of the data indicates that the number of receptors increases while the affinity of transferrin for the receptor remains the same. This rapid increase in the number of receptors at the cell surface appears to be due to a slowing of endocytosis rather than an increase in externalization of the receptor.
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PMID:A rapid redistribution of the transferrin receptor to the cell surface of HL-60 cells and K562 cells upon treatment with dimethyl sulfoxide due to slowing of endocytosis. 229 27

Hemin inhibited 59Fe uptake from transferrin (Tf) by mouse erythro-leukemia cells (MELC) induced for differentiation by hexamethylene bisacetamide (HMBA), but the rate and the extent of 125I-Tf endocytosis was unaffected. Hemin inhibited 59Fe incorporation into heme by a greater proportion than the overall uptake of 59Fe from Tf. Desferrioxamine (DFO) reverted the inhibition of 59Fe transport into MELC caused by hemin. Exogenous 5-aminolevulinic acid (ALA) stimulated 59Fe utilization for heme synthesis in MELC but did not revert inhibition induced by hemin. No evidence for a direct effect of heme on the Tf cycle or iron release was found.
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PMID:The relationship between heme synthesis and iron uptake in erythroid cells. 238 33

We investigated the effects of the iron chelator desferrioxamine on the expression of transferrin receptors (TfR) by CCRF-CEM human T-cell leukaemia and B16 mouse melanoma cells growing in tissue culture. Desferrioxamine (DFOA) enhanced TfR expression when added in the dose range of 10(-5)-10(-4) to CCRF-CEM cells, but was toxic to these cells, the lower concentrations producing a slowing of cell growth with a build up in S-phase, while higher concentrations caused cell death with a block at the G1/S-phase interface. These toxic effects are compatible with its previously reported inhibition of the non-haem iron containing (M2) subunit of ribonucleotide reductase. In marked contrast, DFOA caused the growth of B16 melanoma cells to arrest in G1, without loss of cloning efficiency, and resulted in a fall in TfR expression to approximately 50% of control values. These results suggested that the effects of DFOA on TfR expression were linked to DNA synthesis rather than to a more generalised inhibition of iron-dependent cellular processes. It was subsequently found that inhibition of the M2 subunit of ribonucleotide reductase in CCRF-CEM cells with 5 X 10(-5) M hydroxyurea, which is not an iron chelator, also enhanced TfR expression, as did thymidine and cytosine arabinoside, which have different enzyme targets. By measuring cellular DNA and RNA content simultaneously it was shown that all of these agents caused unbalanced growth, i.e., inhibited DNA synthesis more than RNA synthesis. In contrast, 6-thioguanine was more inhibitory to RNA synthesis, and treatment with this drug caused a fall in TfR expression. Thus, although CCRF-CEM cells treated with DFOA show enhanced TfR expression, similar effects are also seen with other inhibitors of DNA synthesis, provided that RNA synthesis is allowed to continue. These results provide further evidence that the regulation of TfR expression by proliferating cells is specifically linked to DNA synthesis rather than to the iron requirements of other cellular processes.
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PMID:Modulation of transferrin receptor expression by inhibitors of nucleic acid synthesis. 241 49


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