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)

We evaluated eosinophils morphology, physical properties and antileukemic activity in autologous bone marrow transplanted (ABMT) patients treated with subcutaneous recombinant interleukin 2 (rIL-2) and recombinant human interferon alpha 2a (IFN alpha) given as outpatient immunotherapy. All patients receiving rIL-2/IFN alpha therapy developed peripheral blood eosinophilia of 20-40% peaking at 2-4 weeks of therapy. While on rIL-2/IFN alpha therapy the eosinophils became hypodense and hypersegmented. The antibody dependent cell-mediated cytotoxic activity (ADCC) of the eosinophils against the human B-cell lymphoma cell line (Raji) was depressed post-ABMT. Prolonged (28 days) in vivo rIL-2/IFN alpha immunotherapy enhanced ADCC activity of the eosinophils and brought them to normal levels. Similarly, rIL-2/IFN alpha immunotherapy enhanced the depressed cytotoxic activity of neutrophils post-ABMT to normal levels. Thus, eosinophils and neutrophils from rIL-2/IFN alpha-treated ABMT recipients may be targeted toward tumor cells by antibody, and express tumoricidal activity. No effect of rIL-2/IFN alpha was observed on monocyte-dependent ADCC activity which remained normal post-ABMT. We conclude that in addition to their effect on lymphocytes, cytokine-mediated immunotherapy consisting of subcutaneous low doses of riL-2 and IFN alpha may mediate their therapeutic effects in cancer therapy by increasing the number of eosinophils and enhancing the antitumor activity of eosinophils and neutrophils, provided that tumor-specific or tumor-associated antibodies are present.
Leukemia 1994 Aug
PMID:Eosinophils activation in post-autologous bone marrow transplanted patients treated with subcutaneous interleukin-2 and interferon-alpha 2A immunotherapy. 805 77

Twenty-two patients with high risk hematologic malignancies (13 c-ALL, two B-ALL/NHL, four T-ALL, two AML M2, one pre-pre B-ALL) entered a phase I/II trial with cyclic administration of low dose natural interleukin-2/recombinant interferon-gamma (nIL-2/rIFN-gamma) following autologous bone marrow transplantation (ABMT), in order to induce a cytotoxic antileukemic effect. Eighteen patients subsequently relapsed, corresponding to a Kaplan-Meier estimate of disease-free survival (DFS) of 18%. Compared with a historical group of autologous bone marrow recipients who have not received immunotherapy, there is no significant difference according to DFS. Immunophenotyping of peripheral lymphocytes at the onset and end of therapy cycles revealed the most significant mean increase among the NK cell population (262/microliters +/- 51 vs. 354/microliters +/- 36, p = 0.004). However, even CD3 positive T cells rose significantly (591/microliters vs. 689/microliters, p = 0.04). In vitro NK cell activity tested against the NK sensitive myeloid leukemic cell line K562, and LAK cell activity tested against the LAK sensitive Burkitt lymphoma cell line Raji, was only low. An additional in vitro stimulus with nIL2, however, led to a therapy-dependent increase of cytotoxicity which was significant against Raji cells (25% +/- 4 vs. 41% +/- 5, p = 0.0124) indicating that low dose nIL2/rIFN-gamma enhances precursors of potentially cytotoxic cells in vivo.
Leukemia 1994 May
PMID:Low-dose natural interleukin-2 and recombinant interferon-gamma following autologous bone marrow grafts in pediatric patients with high-risk acute leukemia. 818 41

Daudi Burkitt's lymphoma cells have molecules on their surface which can stimulate proliferation of human gamma delta T cells, while Raji, another Burkitt's lymphoma, cannot stimulate human gamma delta T cells. Human peripheral gamma delta T cells, coexpressing the V gamma 9/V delta 2 chains of the T cell receptor, lyse Daudi cells but not Raji cells. Here, we have screened four other Burkitt's lymphoma cell lines (HH514, DG75, Ramos, and Wilson), as well as cells derived from a fresh Burkitt's lymphoma, to see if any of them can be recognized by human gamma delta T cells. Leukemia-derived lines MOLT-4, CEM, and K562 have also been included in these studies. Among the Burkitt's lymphomas tested, only Daudi, DG75, and HH514 could be lysed by V gamma 9/V delta 2+ T cell clones derived from the peripheral blood of healthy donors. These T cell clones were also able to lyse the NK sensitive leukemia lines K562 and MOLT-4. When bulk cultures of peripheral blood mononuclear cells from healthy donors were cultured with different Burkitt's lymphoma or leukemia cell lines, only Daudi stimulated the outgrowth of gamma delta T cells. Similarly, only Daudi cells could stimulate proliferation of gamma delta T cell clones, and the response was enhanced significantly in the presence of interleukin-2. These data and our prior observations showing the use of the V gamma 9/V delta 2 TCR type by Daudi-reactive human gamma delta T cells indicate that Daudi cells are not representative of other Burkitt's lymphoma cell lines.
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PMID:Human peripheral gamma delta T cells are stimulated by Daudi Burkitt's lymphoma and not by any other Burkitt's lymphoma tested. 820 42

Metabolism of benzene results in the formation of multiple metabolites, including hydroquinone (HQ). HQ is a reducing co-substrate for peroxidase enzymes, and the resultant semiquinone and para-benzoquinone (p-BQ) may bind to DNA. The role of peroxidase activation in the formation of DNA adducts by benzene metabolites has not been established. In this study we investigated the role of peroxidase activation in the formation of DNA adducts by HQ and p-BQ in HL-60 cells, human bone marrow (HBM) cells, mouse bone marrow macrophages (MBMM) and the U-937 and Raji leukemia cell lines. Adduct formation was measured by P1-enhanced 32P-postlabeling; peroxidase activity was measured with a spectrophotometric assay. Treatment with p-BQ resulted in the formation of two DNA adducts in all of the cell lines. The DNA adducts were identical in all of the cells, however, the adduct level varied by 80-fold. Treatment with HQ produced one DNA adduct in HL-60 cells, HBM and MBMM; no adducts were detected in U-937 or Raji cells. The HQ-DNA adducts in the three cell lines were identical. The adduct level was highest in the HL-60 cells, followed by HBM and MBMM. There was a statistically significant correlation between peroxidase activity and the formation of HQ-DNA adducts. These results suggest that peroxidase-mediated metabolism is involved in the activation of HQ to form DNA adducts in mouse bone marrow and HBM.
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PMID:Peroxidase activation of hydroquinone results in the formation of DNA adducts in HL-60 cells, mouse bone marrow macrophages and human bone marrow. 824 63

SCL protein production was examined in a variety of hemopoietic cell lines by immunoblotting using specific polyclonal antisera. SCL protein was detected in erythroid, megakaryocyte, mast and early myeloid cell lines, as well as in several lymphoid leukemia cell lines which are known to harbor SCL gene rearrangements. In most cell lines, proteins of molecular weight 49 and 44 kDa were found, however two myeloid cell lines expressed only lower molecular weight species of 24 and 22 kDa. This size discrepancy appeared to be due to cell-specific translational regulation, since overexpression of a retrovirally transfected SCL gene yielded the higher molecular weight forms in most cell lines (GP+E-86, AT2.5, M1) but only the 22 kDa form in the myeloid cell line, WEHI-3B/D+. Overexpression of full-length SCL protein in the lymphoid cell lines, SupT1 and Raji, did not alter cell phenotype and there was no evidence for autoregulation of SCL transcription. The restricted pattern of SCL protein synthesis is consistent with the restricted expression of SCL mRNA documented previously. In addition, the present results indicate that SCL protein size was determined by regulation of translation in a cell-specific manner.
Leukemia 1994 Jan
PMID:The SCL protein displays cell-specific heterogeneity in size. 828 74

We examined the ability of hematopoietic cells to transactivate the HTLV promoter by a transcellular mechanism. HeLa cells containing a CAT reporter gene driven by the HTLV-2 promoter were cocultivated with hematopoietic cells of the B-(Raji), T-(HuT78, Jurkat) and monocyte/promyelocytic (THP-1, U937 and HL60) lineages. Cocultivation with U937 and HuT78 cells constitutively and significantly transactivated the HTLV-2 promoter, while no effect was observed with the other lines. However, activation of other T-cell lines (CEM, Jurkat, Molt-3 and MT-4) with a combination of phorbolester and phytohemagglutinin also resulted in potent transactivation. Supernatant from HuT78 cells exhibited detectable transactivating activity, suggesting that the activation is mediated by a secreted factor(s). This factor also transactivates the HTLV-1 promoter. We used a panel of HTLV-1 LTR deletion mutants to map the responsive elements to this factor(s). Unlike the response element to the HTLV transactivator protein, Tax, which can be mapped to a small region in the enhancer, maximal transactivation by the cellular factor(s) required the complete U3 sequence. Transcellular activation of the HTLV promoter by activated T-cells may play a role in the development of leukemia in HTLV infected individuals.
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PMID:Transcellular activation of the HTLV promoter by human hematopoietic cells. 830 96

The in vitro stimulation of lymphocytes with interleukin-2 (IL-2) generates lymphokine-activated killer (LAK) cells with tumoricidal potential. In this work we studied the cytolytic capacity of LAK cells in 51 acute leukemia patients in complete remission (CR) after chemotherapy (CT), in 24 acute leukemia patients who had undergone autologous bone marrow transplantation (ABMT), and in a control group of 44 normal donors. In the normal donor control group the effect of non-IL-2-activated peripheral blood mononuclear cells (PBMC) against blast cells was always lower than 10% lysis, which we have taken as a lower limit for positive results. In 95% of post-CT patients, the lytic effect of PBMC was negative. LAK cells produced positive results in 82% of normal donors and in 37.5% of post-CT patients. The effect of PBMC against K562, i.e. natural killer (NK) activity, in post-CT patients as well as in post-ABMT patients was reduced in comparison with the average for normal donors. LAK cells from 25% of post-CT patients had no notable activity against K562 or Raji, nor was there any positive effect against autologous blast cells. In the rest (75%), one-half generated positive activity. We did not observe any correlation between lytic activity in PBMCs or in LAK cells, nor did we observe significant differences between lytic activity in patients with acute lymphoblastic leukemia (ALL) and those with acute myeloblastic leukemia (AML), or between patients who had undergone CT and those receiving ABMTs. These results support the use of IL-2 as a treatment against minimal residual leukemia.
Leukemia 1993 Sep
PMID:Generation of LAK cells in vitro in patients with acute leukemia. 837 85

The capacity of alpha-interferon (alpha-IFN) to induce lymphokine activated killer (LAK) cytotoxicity in the absence of interleukin-2 (IL2) has prompted us to test whether or not its ability to reduce dramatically the number of Ph1+ clones in chronic myelogenous leukaemia (CML) patients is in part mediated through the generation of natural killer (NK) or LAK activity. The latter were tested using NK-sensitive (K562) and NK-resistant (Raji) cell lines in a target-cell colony-growth inhibition assay. Effector cells (E) were patient blood mononuclear cells (MC) without in vitro activation prior to their coculture with targets (T). Out of 16 patients tested so far, three failed to undergo cytogenetic remission under alpha-IFN therapy. No NK nor LAK cells could be detected in the MC from two of them while the other displayed NK activity within upper normal limits. 13 patients underwent complete (eight) or partial (five) cytogenetic remission together with significantly high NK and/or LAK activity as compared to normal controls. These observations could favour the hypothesis of an indirect effect of alpha-IFN on leukaemic cells, mediated by cells involved in immune surveillance.
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PMID:Endogenous lymphokine activated killer cell activity and cytogenetic response in chronic myelogenous leukaemia treated with alpha-interferon. 845 70

The LAZ3/BCL6 gene on chromosome 3q27 is recurrently disrupted in B-cell non Hodgkin's lymphomas by translocations involving immunoglobulin genes or other chromosome regions. We have studied the t(3; 11) (q27; q23) translocation, present in a B-cell leukemia cell line (Karpas 231). As a consequence of this translocation, a LAZ3 chimeric transcript was created by fusion, 5' to the LAZ3 exon 2, with a transcribed sequence identical to BOB1/OBF1, a B cell-specific coactivator of octamer-binding transcription factors, recently described. Nucleotidic sequence of a nearly full-length cDNA of the BOB1/OBF1 gene revealed particular features in the 3' untranslated region of the gene, including pyrimidine-rich sequence repeats, an Alu motif, and a polymorphic [CCTT] tetranucleotide microsatellite. Two A to G transition mutations were also detected in the coding region of one allele of a lymphoma B-cell line, Raji, leading to 2 amino-acid changes in the C-terminal region. Due to its cell-specificity and role as a coactivating transcription factor, chromosomal translocation and/or perhaps point mutation of BOB1/OBF1 may contribute to B cell tumorigenesis.
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PMID:Fusion of the LAZ3/BCL6 and BOB1/OBF1 genes by t(3; 11) (q27; q23) chromosomal translocation. 857 89

We have used two methods to evaluate the level of expression of Gb3Cer in several human leukaemia/lymphoma cell lines representative of the myeloid (K562, KG-1, HL-60, and lymphoid (Reh, Daudi, Raji, RPMI 8226, CCRF-CEM, MOLT-4) lineages blocked at varied stages of differentiation. TLC immunostaining of glycolipid extracts with a monoclonal antibody, 12-101, and FACS analysis with the same antibody were used to demonstrate that the expression of Gb3Cer in neoplastic myeloid and lymphoid cells is both lineage and differentiation dependent. As a possible control point in the regulated expression of Gb3Cer we have investigated the first committed step in the synthesis of globo series glycosphingolipids that involves UDP-Gal:LacCer alpha (1,4)-galactosyltransferase (alpha 1,4GalT). We present the first characterization of this enzyme in a human myeloid cell line using an ELISA-based assay, which was subsequently used to measure alpha 1,4GalT activity in the human leukaemia/lymphoma cell lines. In general, there is a positive correlation between the levels of endogenous Gb3Cer and the level of the alpha 1,4 GalT activity. However, in two cases (KG-1 and CCRF-CEM) the level of enzyme activity did not correspond to the level of Gb3Cer expression.
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PMID:Alpha 1,4galactosyltransferase activity and Gb3Cer expression in human leukaemia/lymphoma cell lines. 859 60


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