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 evaluate the modulatory effects of trace metals on lymphocyte growth and maturation, thymidine uptake (TU), protein, ATP, Fe, Cu, Zn, ferritin, CD3, CD4, CD8 antigens, surface transferrin receptors (TFR) and interleukin 2 receptors (IL2R) were assessed in normal and T cell leukemia human lymphocytes, cultured in media with varying Fe, Cu and Zn concentrations [Me]. In normal lymphocytes in media with optimal [Me], all values increased significantly after PHA stimulation, except for intracellular metal concentration and CD3+, CD4+, CD8+ cells which were unchanged. In media with low or high [Me], all parameters except for CD8+ cells were decreased. In unstimulated ALL lymphocytes grown in media with optimal [Me], TU, protein, ATP, CD4+, Fe, Cu and ferritin were higher and Zn and CD8+ lower than in unstimulated normal cells: they did not change after PHA stimulation, except in media with low [Me], in which they approached the values of stimulated normal lymphocytes. TFR and IL2R for ALL cells were high in all media: IL2R but not TFR increased after PHA stimulation. No relationship between IL2R and TFR was demonstrable in any media. We conclude that the response of normal lymphocytes to stimuli is sensitive to variation in trace metals, whereas this response, absent in ALL lymphocytes, reappears only in media with low [Me] and is independent from TFR.
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PMID:Trace metals, surface receptors and growth of human normal and leukemic lymphocytes. 326 16

Cells of the myelomonocytic leukemia cell line RC-2A were studied for their ability to synthesize clotting-promoting and fibrinolytic factors. The cells were observed to generate procoagulant activity (PCA) in readily measurable quantities. Incubation of RC-2A cells with phorbol myristate acetate (PMA; 3 ng/ml) or phytohemagglutinin (PHA, 10 micrograms/ml) for 18 h resulted in a 4-5-fold increase in PCA relative to unstimulated control. The PCA of RC-2A cells was tissue factor-like in that it was dependent on factor VII but not on factors VIII or IX. RC-2A cells also produced plasminogen activator (PA). Secreted PA was approximately 70% of the PA of an identical number of human monocyte-derived macrophages; fresh isolated monocytes synthesized virtually no PA. Compared to macrophages, RC-2A cells secreted less or no PA-inhibitors. Lysates of RC-2A cells contained over three times more PA than lysed macrophages. Stimulation of the cells with lectins (PHA, concanavalin A) or PMA was followed by a modest (2-3-fold) increase in PA. Enzyme immunoassay with antibodies to urokinase (u-PA) or tissue-type PA (t-PA) identified the RC-2A plasminogen activator as being of urokinase type.
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PMID:Cells of the human myelomonocytic line RC-2A synthesize tissue factor-like procoagulant and urokinase-type plasminogen activator. 329 13

Twenty-three patients with hairy-cell leukaemia (HCL), six of whom were previously splenectomized, were treated with alpha-interferon (alpha-IFN) 3 MU per day for 3-6 months and then with 3 MU three times per week for at least 3 further months. Seven patients (two splenectomized) showed a complete response (CR), 11 patients achieved a partial response (PR) and the remaining five experienced only a minor response (MR). All seven patients who achieved a CR are still in CR after 10-21 months from the onset of the disease. Among the 11 PRs, five showed an increase in the number of circulating hairy cells during the follow-up; they were re-started on alpha-IFN and an improvement of the haematological values was again obtained. One patient who achieved only a MR died after 1 month therapy because of severe infection. Following treatment with alpha-IFN, the improvement or normalization of the peripheral blood counts was paralleled by an improvement of the immunologic surface markers, as determined by monoclonal antibodies, and by an improvement of the response to PHA and of the natural killer activity. These findings, coupled to the mild drug-related toxicity observed, confirm that treatment with alpha-IFN represents a safe and effective therapeutic approach for both splenectomized and non-splenectomized HCL patients.
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PMID:Treatment of hairy-cell leukaemia with alpha-interferon (alpha-IFN). 335 6

In an agar-liquid double-layer colony assay in which myeloid leukemia colony-forming cells require the presence of both the lectin PHA and CSF for in vitro proliferation, colony formation of bone marrow cells derived from patients with a myelodysplastic syndrome (MDS) was studied. In five of 14 MDS and all five leukemic transformed MDS cases, colony formation was found to require both PHA and CSF. Three of these five PHA-dependent MDS cases progressed to overt leukemia within 1 year, one progressed from RA to RAEB, and one patient received AML chemotherapy. PHA-dependent colony formation was associated with higher bone marrow blast counts, but not directly to FAB type or cytogenetic abnormalities. In nine other MDS cases only CSF was required for colony formation. In these PHA-independent cases the course of the disease was stable during the observation time (5-17 months). Two types of colonies were observed in this in vitro system: colonies adherent and colonies nonadherent to the agar underlayer. The former consisted of terminally differentiated myeloid cells, and the latter comprised immature cells. This suggests that the percentage of adherent colonies formed in vitro may be used as a measure for the maturation defect in MDS. However, no correlation was found between the percentage of adherent colonies and progression to leukemia of the MDS cases. Our findings suggest that the dependency on PHA for in vitro colony formation of colony-forming cells in MDS is predictive for the progression to leukemia. However, the in vitro differentiation capacity has no apparent prognostic significance.
Leukemia 1988 Jul
PMID:In myelodysplastic syndromes progression to leukemia is directly related to PHA dependency for colony formation and independent of in vitro maturation capacity. 339 24

In groups of 26 patients with myeloproliferative disorders (MPD), 8 with chronic myelogenous leukaemia (CML); 8 with polycythaemia vera (PV); 10 with essential thrombocythaemia (ET); and 6 patients with reactive thrombocytosis (RT), we studied the growth characteristics of bone marrow CFU-M in agar culture. The bone marrows from all the patients with MPD formed so called endogenous CFU-M colonies, in the absence of PHA-LCM, that increased in a dose-dependent manner with the addition of increasing concentrations of normal human AB-citrated plasma (NH-ABCP), while the bone marrows from all the patients with RT and from healthy controls formed few or no endogenous CFU-M colonies. In MPD, the endogenous CFU-M growth was enhanced by normal T cells in a dose-dependent fashion, and was decreased with the depletion of T cells from the marrow cells. These results suggest that the formation of endogenous CFU-M colonies is caused by hypersensitivity of CFU-M in MPD to NH-ABCP, which may contain a small amount of Meg-CSF, and/or by in vitro T cell stimulation. Among MPD, the endogenous CFU-M growth in ET was significantly lower than that of other MPD patients; however, the total number of ET CFU-M grown in the presence of PHA-LCM was the highest. These data show that the bone marrow CFU-M in MPD are heterogeneous with respect to in vitro growth pattern or sensitivity to exogenous Meg-CSF.
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PMID:Heterogeneity of in vitro growth pattern of megakaryocyte progenitors (CFU-M) in myeloproliferative disorders. 341 10

The effect of retinoic acid (RA) alone and in combination with cytosine arabinoside (Ara-C) on differentiation of fresh human myeloid leukaemic cells from patients with AML was studied. Cells from six patients: three with acute myelomonocytic leukaemia AMMoL and three with acute monoblastic leukaemia AMoL with a percentage of blasts greater than 70, were treated in an in vitro primary suspension culture with retinoic acid (10(-7) M), cytosine arabinoside (100 ng/ml) or both in combination. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in RPMI 1640 culture medium supplemented with 20 per cent fetal bovine serum and 10 per cent (PHA-LCM) phytohaemagglutinin leucocyte conditioned medium and incubated for 6 days at 37 degrees C in a humidified incubator containing 5 per cent CO2 in air. Morphological and functional differentiation into terminal mature elements was induced in all leukaemia cells of the six patients following exposure to the combination of both agents. These results suggest the potential usefulness of the combination of a differentiating agent (retinoic acid) and an antileukaemic drug (cytosine arabinoside) in the treatment of acute myeloid leukaemias: AMMoL and AMoL. This combination warrants a clinical trial.
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PMID:Retinoic acid alone and in combination with cytosine arabinoside induces differentiation of human myelomonocytic and monoblastic leukaemic cells. 342 32

The effects of combinations of dipyridamole, an effective blocker of the salvage pathway of DNA synthesis, and 8 types of anti-cancer drugs on the growth of human T, B and myeloid leukaemia/lymphoma cell lines in vitro were examined. In combinations, dipyridamole and vincristine (VCR), and dipyridamole and vindesine had synergistic inhibitory effects. Dipyridamole reduced the efflux of VCR from cells and enhanced their VCR accumulation in a dose-dependent manner at concentrations of up to 10 microM in the lymphoid cell lines, MOLT-3 and BL-TH, and of up to at least 20 microM in the myeloid cell line, ML-1. Dipyridamole also enhanced the accumulation of VCR in PHA-stimulated and un-stimulated lymphocytes of normal donors, but efflux of VCR was more rapid from normal lymphocytes than from cultured cell lines. It is proposed that combination therapy with dipyridamole plus VCR should be effective in the treatment of leukaemia and lymphoma.
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PMID:Synergistic inhibitory effects of dipyridamole and vincristine on the growth of human leukaemia and lymphoma cell lines. 347 94

Phytohemagglutinin and its isolectins PHA-E4 an PHA-L4 act antiproliferatively on an actively dividing leukemia T-cell line. Both PHA and the isolectins caused an increase in soluble protein kinase C (PK-C) activity without a corresponding decrease in particulate activity. The increase was at a maximum after 10 min and the soluble kinase activity remained high for at least 3 h. There was no direct correlation between the observed antiproliferative potency of the 2 isolectins and their ability to initially affect the distribution of PK-C activity.
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PMID:Antiproliferative response of human leukemic cells. Modulation of cytosolic protein kinase C activity by phytohemagglutinin. 348 41

Recent genetic studies of the murine chromosome 17 have demonstrated that many genes encode class I antigens, most of which are still not detected serologically; most of these genes belong to the Tla region. Five human alloantisera were selected from 383 female sera and were further studied using a panel of peripheral blood lymphocytes (PBL), B lymphocytes (BL), and PHA activated lymphocytes (PHA-L) from the same blood donors. After intensive platelet absorption, the five sera still reacted positively by a complement-dependent cytotoxicity technique with PHA-L, but negatively with PBL and BL. The antigens detected by these antibodies segregated with an HLA-A allele and were assumed to belong to the class I antigen series as they could be blocked by a turkey anti-beta 2 microglobulin serum. They were found on some lymphocyte populations: PHA-L, common acute lymphoblastic leukemia (cALL) cells, and (preliminary results) a small subpopulation of PBL cells (mostly NK cells), but were not found on chronic lymphocytic leukemia (CLL) cells, T and early T acute lymphoblastic as well as myeloblastic leukemia cells. Kinetic studies showed that several hours of culture with PHA were necessary for the antigen to be expressed. These results show that the antigens described do not belong to the classic HLA antigen series but could be considered to belong to the human Qa-like antigens or to be the human counterpart to the second murine H-2K locus antigens.
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PMID:New human MHC class I antigens segregating with HLA-A antigens detected on some lymphocyte subpopulations. 348 86

Methimazole (MM), an antithyroid drug, was examined for its ability to modulate immune functions. The increase in [3H]thymidine incorporation in plant mitogen-stimulated lymphocytes and augmentation of NK cell activity by MM were used as a measure of the immunomodulatory activity of MM. The results demonstrated that lymphocytes from 5 different donors had a mean increase of 632% of [3H]thymidine incorporation in the presence of MM at a concentration of 114.2 micrograms/ml (P less than 0.005). Lymphocyte response to PHA, Con A or PWM was potentiated by 27 to 482% in the presence of MM. The MM mediated increase in lymphocyte proliferation was more obvious in cases where the mitogenic stimulation was low. Lymphocyte cytotoxicity to both K562 cells and malignant B cells was also augmented when lymphocytes were cultured in the presence of MM. A maximal effect was observed when lymphocytes were treated with a concentration of 20 micrograms/ml of MM for 12-16 hr. Maximum augmentation was usually exerted when the NK cell activity of cultured lymphocytes was low. This was particularly seen with lymphocyte from cultured B cell leukemia (3163).
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PMID:Effects of methimazole on human lymphocyte proliferation and natural killer cell activity. 360 1


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