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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The K562 cell line provides a unique population of primitive human myeloid leukaemia cells which can be induced to differentiate along the erythroid, granulocytic, macrophage and megakaryocytic lineages in response to several agents. Cytarabine is not only the most widely used drug in the treatment of myeloid leukaemia but also the most effective agent in K562 cells. The effects of five recombinant human cytokines - interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-alpha, interferon-beta and interferon-gamma on cytarabine-induced growth inhibition and differentiation of K562 cells was studied in liquid suspension cultures. GM-CSF and to a lesser extent IL-3 enhanced the antiproliferative effect of cytarabine in K562 cells, whereas the three interferons reduced it. The efficacy of cytarabine in inhibiting the growth of K562 cells was doubled by its combination with GM-CSF or IL-3 but was halved by its combination with interferons. The five cytokines did not significantly affect cytarabine-induced erythroid differentiation of K562 cells. The present results appear to favour the use of GM-CSF and IL-3 but not of interferons in future treatment strategies based on a combined cytokine and chemotherapy approach for myeloid leukaemia.
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PMID:Effects of recombinant human cytokines on cytarabine activity in K562 human myeloid leukaemia cells. 176 Sep 44

Proliferative and interleukin responses to T-cell mitogens such as concanavalin A (Con A) were rapidly and progressively reduced in BALB/c mice infected with the Friend leukemia complex (FLC) or its helper, Friend murine leukemia virus (F-MuLV). In contrast, a combination of the protein kinase C activator phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) and the Ca++ ionophore A23187 elicited a normal lymphoproliferative response up to 8 days postinfection (p.i.) and normal interleukin-2 (IL-2) and interferon-gamma responses up to day 14 p.i. Exogenous IL-2 failed to restore the lymphoproliferative response of infected cells regardless of the stimulation used. These results showed that the T-cell deficits may be at least partly attributable to a derangement of the signal transduction pathway leading to activation. Spleen cells passed through nylon wool columns reacquired a normal responsiveness to Con A +/- TPA up to 14 days p.i. The latter finding suggests that the alterations in signal transduction are not caused by primary defect of the responder-T cells but may result from an extrinsic suppressive mechanism.
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PMID:Alterations of T-cell functions during Friend leukemia complex infection: defective signal transduction? 181 Mar 22

We investigated the effects of interferon-gamma (IFN-gamma), phorbol myristate acetate (PMA), and dibutyryl cAMP (Bt2cAMP) on Fc gamma R subtype expression on a human eosinophilic leukemia cell line, EoL-3. Unstimulated EoL-3 cells expressed Fc gamma RII as determined by monoclonal antibody (mAb) IV-3, whereas there was little or no Fc gamma RI and Fc gamma RIII expression as determined by mAbs 32.2 and 3G8, respectively. IFN-gamma induced Fc gamma RI expression, and Bt2 cAMP, which did not induce Fc gamma RI expression by itself, showed an additive effect on IFN-gamma-induced Fc gamma RI expression. Fc gamma RII expression was augmented by IFN-gamma, PMA, and Bt2 cAMP. Bt2 cAMP also showed an additive effect on IFN-gamma-augmented Fc gamma RII expression. Fc gamma RIII expression could be induced only by IFN-gamma plus Bt2 cAMP. H-7, a protein kinase C (PK-C) inhibitor, suppressed the enhancement of Fc gamma R subtype expression induced by these reagents. These results show that Fc gamma R subtype expression on EoL-3 cells is regulated differently in each subtype and that cAMP and PK-C play important roles in the regulation.
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PMID:Regulation of Fc gamma receptor subtype expression on a human eosinophilic leukemia cell line EoL-3: participation of cAMP and protein kinase C in the effects of interferon-gamma and phorbol ester. 184 82

A recombinant human interferon-gamma (IFN-gamma) was added to the clonal and suspension cultures of bone marrow (BM) cells from three patients with refractory anemia with excess of blasts (RAEB) before and after IFN-gamma therapy. IFN-gamma inhibited the hematopoietic progenitor cell growth from normal BM in one patient. In the remaining two patients with RAEB, IFN-gamma at lower concentrations (10-10(2) U/ml) consistently enhanced the growth of hematopoietic progenitors. The addition of IFN-gamma to suspension cultures promoted cellular differentiation in all three cases, as evidenced by persisting cytogenetic changes, Auer-rod containing maturing cells and cytochemical studies. Although IFN-gamma therapy resulted in partial or minor responses, these findings suggest the potential of IFN-gamma to act as an inducer of differentiation in myelodysplastic syndromes both in vitro and in vivo.
Leukemia 1991 Sep
PMID:Interferon gamma induces differentiation of cells from patients with myelodysplastic syndromes in vitro and in vivo. 194 31

The characteristic lesion in acute myeloid leukemia (AML) is the failure of myeloid cells to differentiate normally, leading to the accumulation of immature blast cells (BC) in the bone marrow. We determined whether BC and leukemia colony-forming cells (L-CFC) from AML patients could differentiate in vitro after short-term culture with interferon-gamma (IFN gamma), 1,25 dihydroxyvitamin D3 (D3), retinoic acid (RA), tumor necrosis factor-alpha (TNF alpha), and granulocyte-monocyte colony-stimulating factor (GM-CSF). Expression of myeloid differentiation antigens CD15, CD14, CD33, and p124 was determined on the BC by immunofluorescence and on the L-CFC by monoclonal antibody (MoAb) and complement (C')-mediated cytotoxicity followed by cloning in methylcellulose. We found that 26 of 39 (67%) cases demonstrated changes in the expression of myeloid differentiation antigens on the BC, and 6 of 7 (86%) cases showed an altered L-CFC myeloid antigen phenotype after short-term culture with differentiating agents. Alterations in myeloid antigen expression in the L-CFC population correlated with a reduction in L-CFC cloning potential. In the BC, alterations of myeloid differentiation antigens occurred in a manner consistent with those observed during normal myelopoiesis. For example, CD14 antigen expression (a late-stage monocyte antigen) increased on BC from 12 of 39 (31%) cases, and p124 (an antigen expressed both by myeloid progenitor cells and by a subset of monocytes) increased on 15 of 39 (38%) cases. Changes in the expression of CD33 antigens (expressed normally by myeloid progenitor cells and by mature monocytes) on the BC were variable, with 7 of 29 cases (24%) showing a decrease and 7 of 29 cases (24%) showing an increase. When comparisons were made between pairs of differentiation agents that caused the altered expression of an antigen on either the BC or L-CFC of a patient, the majority of changes were in the same direction (either both "increased" or both "decreased"). This suggests that the direction of antigen change is characteristic of the leukemia cell subpopulation for each patient and not of the stimulatory agent. This study demonstrates that cells from more than two thirds of AML cases examined responded to various differentiation agents in vitro as measured by changes in the expression of myeloid cell-associated surface antigens and by alterations in cloning potential of the L-CFC, a finding of potential clinical significance.
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PMID:Induction of differentiation in blast cells and leukemia colony-forming cells from patients with acute myeloid leukemia. 210 8

Exposure of HL-60 promyelocytic leukemia cells to a combination of interferon-gamma (IFN gamma) and 5-fluorouracil (5-FU), at concentrations ineffective by themselves, induced a significant differentiation into monocyte-like cells. This phenomenon was accompanied by a synergistic antiproliferative effect. Further characterization of these two activities of the IFN gamma/5-FU combination on HL-60 cells was carried out. Whereas a brief pretreatment of the cells with IFN gamma followed by 5-FU was sufficient to exert the synergistic antiproliferative action, the effect on differentiation was dependent on a prolonged concomitant exposure to both drugs. In an attempt to gain more insight into the biochemical mechanisms of these phenomena, we have examined the effects of RNA and protein synthesis inhibitors and of cytoskeleton disrupting agents on the actions of IFN gamma. Inhibition of RNA or protein synthesis by actinomycin D or cycloheximide did not prevent the antiproliferative action of IFN gamma nor the induction of monocytic differentiation, yet these two compounds blocked the priming effect of IFN gamma on the potentiation of 5-FU action. Actinomycin D synergistically potentiated the antiproliferative action of IFN gamma. Colchicine, vinblastine, and cytochalasin B, disrupting the microtubular and microfilament structure, did not interfere with the actions of IFN gamma; higher concentrations of the drugs even improved the priming effect. Exogenous thymidine, known to counteract the antiproliferative effect of 5-FU, also blocked the antigrowth action but not the differentiation induced by the IFN gamma/5-FU combination. The results suggest the existence of two different mechanisms of the IFN gamma/5-FU synergism: one governing the antiproliferative action via an effect on thymidine synthetase, inducible by a short-term IFN gamma pretreatment and dependent on de novo RNA and protein synthesis; and the other mediating the induction of differentiation requiring a long-term exposure of the cells to both drugs. From a clinical point of view, drug combinations such as IFN gamma and 5-FU, inducing differentiation as well as inhibiting proliferation, may suggest a new approach to the treatment of leukemia.
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PMID:Mechanism of interaction between interferon-gamma and antineoplastic agent on the differentiation of HL-60 promyelocytic cells. 210 96

We have developed a model system to study immunologically mediated regression of leukemia based on Friend virus-induced erythroleukemias. This system has been used to evaluate the immunotherapeutic activity of macrophages, specifically reactive T-cells (CTL/RFB), lymphokine-activated killer cells and interleukin 2, and tumor necrosis factor alpha and interferon-gamma. In the present studies, CTL/RFB were evaluated for their ability to prevent disease recurrence. Animals with the regressing strain of Friend virus at Day 39 post virus were treated with either one or two injections of 5 x 10(6) CTL/RFB. Animals given one or two injections of CTL/RFB had a significantly lower rate of recurrence than did untreated animals. The helper T-cell component of CTL/RFB was implicated in causing leukemia regression. Interleukin 1 alpha and tumor necrosis factor alpha, multifunctional cytokines with similar biological activities, were evaluated for their ability to suppress leukemic erythroid colony-forming cells and induce regression. Interleukin 1 alpha suppressed the conventional strain of, but not the polycythemia-inducing strain of, Friend virus-leukemic late erythroid colony-forming units and caused only a temporary regression of disease, while tumor necrosis factor alpha suppressed both forms of the disease and with multiple inoculations could cause permanent disease regressions. This system provides an excellent model for examining the efficacy of immunotherapy of leukemias with various mediators and effector mechanisms.
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PMID:Immunotherapeutic approaches to leukemia: the use of the Friend virus-induced erythroleukemia model system. 211 83

Three cases of adult T-cell leukemia (ATL) with cutaneous lesions of disseminated papules or nodules were treated with recombinant human interferon-gamma (IFN-gamma) by intravenous administration. Clinical stage of each case was different, i.e., 1) preleukemic state of ATL (pre-ATL), 2) chronic-type ATL, and 3) crisis-type ATL. We evaluated clinical efficacy of IFN-gamma, and performed immunohistochemical analysis of biopsy specimens derived from cutaneous lesions of the patients both before and during treatment. The case of pre-ATL achieved a complete remission of cutaneous lesions for 18 months. The other cases also obtained clinical responses with a shorter duration, but relapsed while they are still on IFN-gamma therapy. The cutaneous lesions reduced in size during the therapy associated with a decrease in the ratio of Leu3a + 3b (CD4)+ cells in all three cases. After the therapy, Leu7 (HNK-1)+ cells increased in all cases, and LeuM5 (CD11)+ cells did in two. These results suggested that IFN-gamma enhanced tumor immunity although its clinical effect was less clear. Only in the cutaneous lesions of pre-ATL case an increased number of LeuM5+ cells, probably monocyte-macrophage series in host defence, were seen before the therapy. And IFN-gamma was useful for this case after all.
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PMID:[Treatment of adult T-cell leukemia with intravenous administration of IFN-gamma-immunohistochemical studies of infiltrating cells in cutaneous lesions]. 212 Apr 85

To explore agents for differentiation therapy of leukemias, various combinations of cytokines and low-molecular-weight inducers were examined for differentiation-inducing activity toward three kinds of human leukemia-derived cell lines. The strongest differentiation inducing activity on promyelocytic HL60 cells and histiocytic U937 cells was obtained by combining recombinant tumor necrosis factor (rTNF), interferon-gamma (IFN-gamma), retinoic acid (RA), and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3). For myeloblastic ML1 cells, the combination of rTNF, IFN-gamma, and RA had the strongest differentiation-inducing activity.
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PMID:Induction of differentiation of human leukemia cells by various combinations of cytokines and low-molecular-weight inducers. 219 88

We have isolated a subline of the M-07 human megakaryoblastic leukemia cell line, designated M-07e, that requires either interleukin-3 (IL-3) or granulocyte macrophage colony-stimulating factor (GM-CSF) for growth, even in the presence of fetal calf serum. This cell line will not grow long term in any other cytokine although it responds slightly to IL-2, IL-4, IL-6, IL-9, and interferon-gamma. We have used the M-07e subline to develop a quantitative bioassay for the measurement of levels of either GM-CSF or IL-3. This assay is as sensitive to either factor as the human bone marrow colony assay (CFU-GM) or the chronic myelogeneous leukemic (CML) blast cell proliferation assay for these factors and is much more convenient and reliable than either. With this assay, as little as 25-50 pg/ml of either IL-3 or GM-CSF can be detected, a level that should render the assay useful for analysis of these molecules in samples from patients undergoing colony-stimulating factor therapy and from conditioned media from natural sources of the factors. In these cases, neutralizing antisera to each cytokine are required to demonstrate the specificity of the assay. This assay, in combination with quantitative immunoassays, should greatly facilitate the analysis of the roles of IL-3 and GM-CSF in regulating hematopoiesis both in patients and in natural sources of the cytokines.
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PMID:M-07e human leukemic factor-dependent cell line provides a rapid and sensitive bioassay for the human cytokines GM-CSF and IL-3. 227 55


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