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

The role of CD11/CD18 leukocyte adhesion molecules and their ligands in mediating non-major histocompatibility complex (MHC) restricted lymphocyte cytotoxicity is controversial. In order to examine the role of target cell intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of lymphocyte function-associated antigen (LFA-1) (CD11a/CD18), we exposed the human leukemia cell line, HL-60, to a variety of agents implicated in modulating ICAM-1 expression and/or sensitivity to lymphocyte cytolysis. Exposure of HL-60 cells to retinoic acid (RA), interferon (IFN)-alpha, IFN-beta, and IFN-gamma induced protection from lymphokine-activated killer (LAK) cytolysis. Only RA and IFN-gamma induced ICAM-1 expression. Tumor necrosis factor and vitamin D3, which also induced ICAM-1 expression, increased HL-60 sensitivity to LAK lysis. Granulocyte-macrophage colony-stimulating factor also increased sensitivity to LAK lysis; ICAM-1 was not induced. The state of cellular differentiation and expression of class I and II MHC antigens also did not correlate with sensitivity to LAK cytolysis. Exposure of untreated HL-60 cells and HL-60 cells expressing ICAM-1 to monoclonal antibody (mAb) versus ICAM-1 did not modulate LAK sensitivity. Exposure of LAK cells to mAb versus LFA-1 partially inhibited cytolysis; mAb versus CD18 inhibited cytolysis more completely. HL-60 cells were resistant to natural killer lysis; exposure to the various experimental agents did not alter sensitivity. We conclude that leukemic cell sensitivity to LAK cytolysis can be modulated by a variety of agents. Although our results suggest a role for leukocyte CD11/CD18 adhesion molecules in LAK cytolysis, the poor correlation between ICAM-1 expression and sensitivity to LAK lysis suggest that interactions other than LFA-1/ICAM-1 conjugation may be more central to the processes involved.
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PMID:Modulation of leukemic cell sensitivity to lymphokine-activated killer cytolysis: role of intercellular adhesion molecule-1. 136 53

Growth inhibitory (GI) factors for mouse monocytic leukemia cells were previously found in conditioned medium (CM) of a clone of mouse myeloblastic leukemia Ml cells (R1-GI factor) and in CM of mouse lung tissue (L-GI factor). In the present study, the effects of these GI factors on the growth of variant cell lines (Mm-A, Mm-P and Mm-S2) of mouse monocytic line Mm-1 cells were examined. Mm-A are highly leukemogenic to syngeneic SL mice, Mm-P cells are moderately leukemogenic, while Mm-S2 cells have little or no leukemogenicity. The R1-GI factor markedly suppressed the growth of Mm-A cells, whereas it inhibited the growth of Mm-P and Mm-S2 cells only moderately. Recombinant mouse interferon beta (IFN beta) had similar target specificities to those of the R1-GI factor on these variant cells. Moreover, anti-mouse IFN beta antibody completely neutralized the GI activity of the R1-GI factor on Mm-A cells. These results show that the R1-GI factor and mouse IFN beta are very similar and probably identical proteins. The L-GI factor had different target specificities from the R1-GI factor: it showed strongest GI activity on Mm-P cells, moderate GI activity on Mm-S2 cells and weak GI activity on Mm-A cells. Recombinant human interleukin 6 (IL-6) had similar target specificities to the L-GI factor on these Mm-1 variant cells. Furthermore, the L-GI factor could support the proliferation of IL-6-dependent MH60.BSF2 cells. Anti-mouse IL-6 antiserum neutralized the GI activity of the L-GI factor on Mm-P cells. Thus the L-GI factor and mouse IL-6 seem to be closely related and possibly to be identical proteins.
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PMID:Characterization of growth inhibitory factors for mouse monocytic leukemia cells. 154 66

Mice infected with LP-BM5 murine leukemia virus (MuLV) develop a syndrome denoted as murine AIDS. Macrophages harvested from the peritoneal cavities of these mice at 4 or 9 wk postinoculation with LP-BM5 MuLV were analyzed by Northern hybridization for the presence of the defective LP-BM5 virus and their ability to synthesize various cytokines upon induction with Newcastle disease virus (NDV) or (LPS). Neither IFN-alpha or IFN-beta was found to be constitutively expressed in LP-BM5-infected macrophages and in NDV induction studies, and the levels of biologically active IFN-alpha and its mRNA were found to be lower in LP-BM5 MuLV-infected macrophages than in the macrophages from uninfected controls. Similarly, after NDV or LPS induction, the levels of TNF mRNA and TNF protein were significantly lower in LP-BM5-infected macrophages than in macrophages from uninfected mice. The LP-BM5 MuLV-infected macrophages constitutively expressed low levels of IL-1 beta, and when induced with LPS, the relative levels of IL-1 beta were significantly higher in infected than in uninfected macrophages. Although no constitutive expression of IL-6 was detected, the levels of IL-6 mRNA induced with NDV were higher in LP-BM5 MuLV-infected macrophages than in controls. Thus, we found alterations in the expression of selected cytokines in macrophages from mice inoculated with LP-BM5 MuLV rather than a general deregulation of all cytokine expression. These results show that macrophages infected with the defective LP-BM5 virus respond differently to NDV- or LPS-stimulation and suggest that aberrant expression of certain cytokine genes may play a role in the immunopathologic condition in mice with murine AIDS.
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PMID:Aberrant expression of cytokine genes in peritoneal macrophages from mice infected with LP-BM5 MuLV, a murine model of AIDS. 170 89

Ten hairy-cell leukemia patients were treated with interferon beta (IFN-beta) at a dose rate of 2 x 10(6) IU/m2 x 5 days for 4 weeks (induction therapy) and, thereafter, at the same dose three times a week for 11 months (maintenance therapy). The effect of this treatment on serum neopterin, beta 2-microglobulin, (2'-5')oligoadenylate [(2'-5')An] levels, intracellular (2'-5')An values and human Mx protein synthesis was analysed. There were significant rises in serum neopterin and (2'-5')An levels during both induction and maintenance, whereas beta 2-microglobulin levels rose only during induction. Rises in intracellular (2'-5')An were documented mainly during induction, but they were not significantly higher than pretherapy values. IFN beta provoked an increase in human Mx protein synthesis over the entire induction-maintenance period, but was only significantly higher than baseline during induction. All markers proved useful for monitoring the effects of IFN beta dose schedules, but were not predictive of clinical outcome. Natural killer activity and IFN gamma production, which were initially defective, followed a different trend from that of the other factors studied, in that increases were documented only late in the course of therapy when the disease was already in remission.
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PMID:Biochemical and immunological responses of hairy cell leukemia patients to interferon beta. 176 Aug 15

Hairy cell leukemia is a rare, B-cell malignancy uniquely sensitive to the antitumor effects of alpha and beta interferons (IFN). In order to further study the effects of IFN in this disease, we derived a cell line (HC1) from the peripheral blood mononuclear cells of a patient with hairy cell leukemia (HCL). Cells exhibited the typical morphological features of HCL, including the characteristic cytoplasmic projections by light, transmission, and scanning electron microscopy. HC1 cells were of B-cell lineage, as evidenced by immunophenotypic analysis. Although originally TRAP positive, HC1 cells lost this biochemical marker following 3 months in culture. Monoclonality of the cell line was confirmed by a clonal karyotypic abnormality characteristic of B-cell malignancies, and the presence of a single, distinctive fused terminal EBV fragment. The cells formed colonies in soft agar and were tumorigenic in irradiated nude mice. HC1 cells were sensitive to the antiproliferative effects of IFN-a and IFN-beta, but only moderately sensitive to the growth inhibitory effects of IFN-gamma. Incubating the cells in the presence of Type 1 IFN resulted in stabilization of cell numbers, without cellular proliferation or loss. Cell cycle analysis revealed that IFN-alpha resulted in a build-up of cells in the S phase of the cell cycle, suggesting a cytostatic effect of IFN on the growth of these cells. The HC1 cell line provides a model system which will be useful for in vitro studies of the biology and treatment of this disease.
Leukemia 1991 May
PMID:Establishment and characterization of an Epstein-Barr virus spontaneously transformed lymphocytic cell line derived from a hairy cell leukemia patient. 131 27

Thirteen hairy-cell leukaemia patients were treated with IFN-beta (6 X 10(6) IU/m2) for 7 days, alternate weeks, for three cycles. IFN-beta was then continued at the same dose twice a week for 24 weeks. Treatment was discontinued in 2 non-responders and 2 partial responders (1 haem PR, 1 path PR) because of complications unrelated to IFN. The objective response in the nine patients who completed therapy was 66% (1 CR, 3 path PR and 2 haem PR); 2 patients achieved MR. Responses lasted from 5 to 45+ months. Four newly diagnosed patients and 3 in relapse after discontinuation of IFN-beta therapy (6 X 10(6) IU/m2), were treated with a lower dose of IFN-beta (2 X 10(6) IU/m2). The objective response to this dose was 57% (3 path PR, 1 haem PR). Another patient obtained MR. No patient has relapsed 6-12 months after therapy discontinuation. IFN-beta was well tolerated, especially at the lower dose and no chronic toxicity was observed. Therefore IFN-beta may be suggested as an alternative treatment for HCL.
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PMID:Response to intermediate and standard doses of IFN-beta in hairy-cell leukaemia. 223 50

We report that 5 of 19 human malignant glioma cell lines have neither interferon alpha (IFNA) nor interferon beta (IFNB) genes that are detectable by Southern blotting. Of 5 other of these malignant glioma lines that have a single IFNB gene copy, 3 lack the IFNA genes entirely and two have one copy. One of the lines that lacks the IFNA genes entirely but has one copy of the IFNB gene has a rearrangement near the IFNB gene that is most easily interpreted as an insertion of a large segment of DNA (at least 50 kilobases) the 3' end of which is less than 1.3 kilobases 5' to the known regulatory sequences of the IFNB gene. In spite of the rearrangement, IFNB-specific RNA is highly inducible in this line by poly(I)-poly(C). The ability of interferon alpha or interferon beta to inhibit cell growth does not depend upon the presence or absence of the respective gene. This finding adds solid tumors to those tumor cell lines (acute lymphocytic leukemia, chronic myelogeneous leukemia) previously determined to lack the IFNA and IFNB genes (Diaz et al., Proc. Natl. Acad. Sci. USA, 85:5259-5263, 1988).
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PMID:Absence of IFNA and IFNB genes from human malignant glioma cell lines and lack of correlation with cellular sensitivity to interferons. 229 67

The human Mx, an interferon (IFN)-alpha- and IFN-beta-induced 76-kd protein, is a homolog (Mx-homolog) to the murine Mx protein, which is necessary and sufficient to provide adequate resistance against influenza virus in murine cells and in mice. Leukocytes from 36 patients with tumors (chronic myelogenic leukemia, hairy cell leukemia, and malignant melanoma) were monitored for their Mx-homolog content before, during, and after rIFN-alpha-2b therapy. Before therapy, only one patient was slightly positive for Mx-homolog. All 36 patients showed a significant increase of Mx-homolog in their mononuclear cells within the first day of IFN therapy. During therapy, the Mx-homolog levels remained elevated. After cessation of treatment, the Mx-homolog content in the mononuclear cells decreased slowly; within 2 weeks, it was about 20-30% of its value during therapy. However, even after 3 weeks, the Mx-homolog was still detectable. The maximally induced Mx-homolog concentration showed a significant correlation to the IFN dose given in vivo. These data indicate that the Mx-homolog is an excellent marker for monitoring the activity of IFN during IFN therapy. In addition, the in vivo endogenous activation of the IFN system might be detectable by the determination of the Mx-homolog despite the lack of circulating IFN.
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PMID:Emergence and decay of the human Mx homolog in cancer patients during and after interferon-alpha therapy. 238 Jul 45

Interferons (IFNs) have established antitumor action; the mechanism underlying this effect is, however, not yet clear. To probe the possible contribution of inhibition of angiogenesis, we have assessed angiogenesis in the mouse initiated by either human or murine tumor cell lines. Whether test cells were inoculated in the dermis or tumor fragments were grafted onto the cornea, tumor-induced angiogenesis (TIA) was inhibited by IFNs. TIA was also inhibited by the potent IFN inducer polyriboinosinic-polyribocytidylic acid. The effect of IFN was species specific; human IFNs inhibited human tumors and mouse IFNs inhibited murine tumors. This effect suggested that in contrast to other angiogenesis inhibitors, IFNs modulated the signal for angiogenesis produced by the tumor cells. Tumor cells treated in vitro with homologous IFN were significantly (P less than 0.005) less competent to initiate angiogenesis than were untreated cells. Inhibition of angiogenesis was achieved whether vascular response was assessed 1 or 3 days after tumor cell inoculation, suggesting that antiangiogenesis activity was independent of the antiproliferative effects of IFNs. To further substantiate this, L1210 leukemia cells, resistant to the antiproliferative effects of IFNs, were treated with 500 units/ml IFN-beta. IFN had no effect on their proliferation, but in four separate experiments, L1210R cells were impaired in their ability to induce angiogenesis. Thus, inhibition of TIA by IFNs was species specific, occurred at least partly by modulation of the signal inducing angiogenesis, and was expressed in the absence of antiproliferative effects. IFNs also inhibited immunologically induced angiogenesis, whether initiated by allogeneic lymphocytes (LIA) or by the mouse's own T-cells in response to an exogenous antigen (sheep RBC). LIA was markedly suppressed by treatment of host mice with homologous IFN-beta. For example, mean vessel counts induced by allogeneic mouse lymphocytes were decreased from 22.8 +/- 1.4 (SE) to 12.5 +/- 0.8 (P less than 0.0001); mouse IFN-beta had no corresponding effect on xenogeneic human lymphocytes (mean vessel counts decreased to 21.7 +/- 2.6 from 22.7 +/- 2.0). Treatment with human IFN-alpha, -beta, or -gamma in vitro or host mice in vivo reduced the ability of inoculated human peripheral blood lymphocytes to initiate xenogeneic LIA. Inhibition of LIA required a lower dose and/or a shorter incubation period than that needed to modulate TIA. Treatment of the donor of the allogeneic spleen cells in vivo with murine IFN or inducers also resulted in lesser LIA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibition of angiogenesis by interferons: effects on tumor- and lymphocyte-induced vascular responses. 244 62

Hairy cell leukemia (HCL) is a pre-plasma B cell tumor which responds to interferon (IFN)-alpha therapy. In vitro, B cell growth factor (BCGF) can induce proliferation of hairy cells. We have investigated the effect of in vitro and in vivo treatments with different recombinant IFN on the capacity of hairy cells to proliferate in response to human BCGF. In vitro treatment of leukemic cells from HCL patients with recombinant IFN-alpha-2 (5/5 cases) or IFN-beta (4/5 cases) resulted in a marked inhibition of the BCGF-dependent response. This suppressive effect was obtained with IFN concentrations of 1000, 100 IU/ml, and even occasionally 10 IU/ml. In contrast, no such inhibition was observed with IFN-gamma, despite the presence of specific IFN-gamma receptors on hairy cells at densities similar to receptors for IFN-alpha/beta. The IFN-alpha-induced suppression of the proliferative response of hairy cells to BCGF was also observed in vivo in two patients within 6-12 hr after administration of single doses of IFN-alpha. When hairy cells were maintained in culture for 1 week, they recovered their capacity to be stimulated by BCGF. This reversion was also shown in vivo in hairy cells isolated 1 week after IFN administration. Since in vivo growth of hairy cells could possibly result from the autocrine secretion of BCGF, we propose that the therapeutic effect of IFN-alpha on HCL may be due in part to an inhibition of such autocrine loop.
Leukemia 1987 Aug
PMID:Proliferative response of hairy cells to B cell growth factor (BCGF): in vivo inhibition by interferon-alpha and in vitro effects of interferon-alpha, -beta, and -gamma. 244 36


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