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 analyzed the maintenance of acute myeloid leukemia clonogenic cells (AML CFU-L) in liquid culture in the presence of five potential differentiation inducers: trans-retinoic acid, 1,25-dihydroxy vitamin D3, interferon gamma, granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), used singly and with two combined. The culture medium contained either fetal bovine or human serum from normal donors. CFU-L recovery after 7 days was compared to that observed in control cultures. Of AML cases and HL60 cells, 11/15 displayed greater than 50% CFU-L reduction in response to one or more inducers. In 8/9 responsive cases that underwent the nitroblue tetrazolium (NBT) reduction test, an increase in the percentage of functionally mature (NBT-positive) cells was detected. The combination of retinoic acid with interferon gamma was most effective in reducing CFU-L recovering (8 responsive/15 AML cases), G-CSF and M-CSF displayed either inhibitory or stimulatory activity in different AML cases. The type of serum employed generally did not affect the response to inducers of differentiation. No significant inhibition of the recovery of granulocyte-macrophage colony-forming units was determined by the five inducers in experiments with three normal bone marrow samples. Our experiments indicate that biological differentiation inducers can reduce AML CFU-L self-renewal and increase the proportion of differentiated cells at concentrations that do not affect normal myelopoiesis and could be achieved during treatments in vivo.
Leukemia 1992 Feb
PMID:Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological inducers of differentiation. 137 69

Leucocyte adhesion molecule 1 (LAM-1) participates in the binding of human leucocytes to high endothelial venules in peripheral lymph nodes. Other adhesion receptors which are involved include CD44 and the integrin family, CD11/CD18. In this study, B-cell chronic lymphocytic leukemia (B-CLL) cells were examined for the expression of these adhesion molecules, and for the way in which cytokines are able to modulate the levels of these receptors. B-CLL cells express significant but variable levels of LAM-1 and high levels of CD44. In contrast, these cells exhibit very low or absent amounts of surface CD11a, CD11b, or CD11c. Most CLL cells expressed no detectable levels of intercellular adhesion molecule-1 but some cases show levels of up to 30%. Following 24 h incubation with interferon alpha (500 U/ml), surface LAM-1 expression on peripheral blood E-negative cells from CLL patients rose to 330 +/- 127% of levels on control cells incubated with medium alone (n = 13, p less than 0.0005). Interleukin 4 (1 ng/ml) and interferon gamma (100 U/ml) also increased surface LAM-1 levels on these cells to 218 +/- 119% (n = 8, p less than 0.001) and 245 +/- 116% (n = 5, p less than 0.001) of control levels respectively. Induction of LAM-1 expression occurred over 48 h (greater than 50% of the increase was seen in the first 24 h) in a dose-dependent manner and required protein synthesis. The induction of LAM-1 expression on the malignant cells may, by altering the homing behaviour of these cells, relate to the reduction in peripheral leukaemic cells seen following treatment with interferon alpha in CLL.
Leukemia 1992 May
PMID:Cytokine induction of leucocyte adhesion molecule-1 (LAM- 1) expression on chronic lymphocytic leukaemia cells. 137 97

Fourteen children (ages 2-15 years) with acute leukemia in relapse were treated with daily recombinant interferon gamma for 14 days by subcutaneous injections at fixed dose levels of 0.1, 0.25, 0.5, or 0.75 mg/m2 (1.0, 2.5, 5.0, or 7.5 x 10(6) units/m2) without intrapatient escalation. Patients received a second 14-day course of therapy followed by thrice weekly administration unless there were signs of progressive disease or grade 3 or 4 toxicity. Side effects in the 13 evaluable patients included fever (n = 10), fatigue (9), decreased Karnofsky performance score (8), hypertriglyceridemia (8), myalgia (5), weight loss > 5% (4), elevated liver transaminases (4), and abdominal pain (3). There was only one grade 4 toxicity: one of the six patients at the 0.5 mg/m2 dose level developed reversible acute renal failure. One patient died of gastrointestinal hemorrhage due to disease-related refractory thrombocytopenia. One child had an oncolytic response and two others stable disease for 138 and 148 days. An appropriate dose level for phase II studies in children is 0.5 mg/m2 per day.
Leukemia 1992 Nov
PMID:Phase I study of recombinant human interferon gamma in children with relapsed acute leukemia. 143 1

A T cell line from mononuclear cells in the synovial fluid of a patient with polyarthritis was established. The T cell line reacted with serum samples positive for antibodies to human T cell lymphotropic virus type I (HTLV-I) and with monoclonal antibody to HTLV-I p19. In Southern blotting with an env-pX-LTR HTLV-I probe and digestion of T cell line DNA with the restriction enzymes ClaI, DraI, and PstI generated fragments that were identical to those found in two HTLV-I infected T cell lines established from adult T cell leukaemia or HTLV-I associated myelopathy. The T cell line expressed CD2, CD3, CD4, CD45RA, CD29, HLA-DR, CD25, and CD26 antigens, but not CD8 and CD20 antigens. Large amounts of interleukin 6, interferon gamma, and tumour necrosis factor alpha were secreted in the culture supernatants of this cell line. This line helped immunoglobulin production by B cells, but not K562, Raji, and synovial cell lysis.
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PMID:HTLV-I associated arthritis: characteristics of an HTLV-I virus infected T cell line from synovial fluid. 161 38

A child with acute myelogenous leukemia who relapsed three months after an allogeneic bone marrow transplant received intermediate-dose cytarabine followed by interleukin 2 (IL-2). Complete remission was achieved after the first cycle of IL-2. Five more combined cycles of cytarabine and IL-2 were given over the next year, during which remission has persisted. IL-2 therapy affected serum tumor necrosis factor (TNF), interferon gamma (IFN gamma) and soluble IL-2 receptor (sIL-2r) levels. In vitro cytotoxicity against leukemia cell lines and recipient leukemia cells was also increased.
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PMID:Therapy of advanced acute myeloblastic leukemia with cytarabine and interleukin 2. 191 Jan 27

Cytolysis of leukemic cells by peripheral blood-derived macrophages was examined by means of an in vitro 111In release assay. Monocytes prepared on culture dishes lyse YK-M2. However, when monocytes were cultured in vitro and transformed into macrophages, they lost most of their lytic activity. The addition of human recombinant interleukin-2 (rIL-2) on day 5 in culture enhanced the lytic activity significantly. Similarly, treatment of macrophages with human recombinant interferon gamma (rIFN-gamma) promoted the lysis of YK-M2 and K-562, although the extent of lysis was smaller than that by rIL-2. Macrophages activated with rIL-2 and rIFN-gamma also lysed human leukemic cells. Activated macrophages lysed leukemic cells of acute myelocytic leukemia more than acute lymphocytic leukemia cells. Macrophages derived from the peripheral blood of patients with leukemia were examined for their lytic activity against YK-M2. The patient's macrophages lysed more YK-M2 than did control macrophages when they were activated with rIL-2 and rIFN-gamma. The macrophages of two patients also demonstrated autologous leukemic cell lysis.
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PMID:Lysis of human leukemic cells by monocyte-derived macrophages activated with interferon-gamma and interleukin-2. 249 59

The authors have investigated the regulation of mouse major histocompatibility complex (MHC, H-2) class I gene expression of tumors growing in the brain, by using T-cell lymphoma (Moloney leukemia virus-induced YAC-1 of A/Sn mouse origin) and its cell surface H-2 negative variants, A. H-2- and beta 2m-. FACS analysis showed that low H-2 expressing YAC-1 markedly increased H-2 Kk, Dd and beta-2 microglobulin (beta 2m) induction on the cell surface after intracerebral (i.c.) passage, while there was no change in phenotypical expression of both A. H-2- and beta 2m-. Southern and Northern blot analyses revealed that the enhancement of H-2 class I expression in YAC-1 was due to transcriptional control of H-2 DNA genes. beta 2m- was confirmed to lack beta 2m- gene, causing cell surface H-2 negative expression. Immunoprecipitation method showed that, despite increase in mRNA of the H-2 gene, A. H-2- disclosed no class I H-2 expression because of the incapability of intracellular association of polypeptides between H-2 and beta 2m in the post-translational level. The H-2 class I expression on YAC-1 cells could also be induced by interferon gamma (IFN) in a dose-dependent manner in the range of 1 to 100 U/ml. At 100 U/ml, the H-2 inducing effect, regulated at the transcriptional level, was comparable to that observed after i.c. passage. In contrast, the A. H-2- and beta 2m- remained completely negative after IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Molecular analysis of mouse major histocompatibility complex class I gene expression of tumors growing in the brain]. 250 51

The therapeutic potential of recombinant interferon gamma (IFN gamma) alone or in combination with two cytotoxic drugs - 5-fluorouracil (5-FU) and cytosine arabinoside (Ara-C) - was studied in vitro on two myeloid leukemia systems: HL60 promyelocytic cell line and chronic granulocytic leukemia (CGL) progenitor cells. When applied individually, IFN gamma and the drugs inhibited in a dose-dependent manner HL60 cell colony formation in semisolid culture. Moreover, IFN gamma or the cytotoxic drugs dose-dependently reduced the colony formation of CGL progenitor cell in agar. When added in combination, IFN gamma potentiated synergistically the inhibitory action of 5-FU in both systems. The most pronounced potentiation was detected at concentrations of 0.5 microgram/ml 5-FU and 50 U/ml IFN gamma. On the contrary, the antiproliferative effect of Ara-C was enhanced only subadditively when combined with IFN gamma. In view of the present findings, which are supported by new evidence from the literature, the use of 5-FU in leukemia should be reconsidered. The results further imply the potential value of combined treatment of 5-FU and IFN gamma in leukemia.
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PMID:New combination of 5-fluorouracil and interferon-gamma effective against human myeloid leukemia in vitro. 251 May 79

The present investigation demonstrates that leukoregulin, a cytokine secreted by natural killer (NK) lymphocytes up-regulates the sensitivity of tumor cells to lymphokine-activated killer (LAK) cell cytotoxicity. It has been previously established that leukoregulin increases the sensitivity of sarcoma, carcinoma and leukemia cells to natural killer (NK) cell cytotoxicity. Tumor cells were treated with leukoregulin for 1 h at 37 degrees C and tested for sensitivity to NK and LAK cytotoxicity in a 4-h chromium-release assay. NK-resistant Daudi, QGU and C4-1 human cervical carcinoma cells became sensitive to NK cytotoxicity after leukoregulin treatment, and their sensitivity to LAK was increased two- to sixfold. Y-79 retinoblastoma cells, which are moderately sensitive to NK and very sensitive to LAK, became increasingly sensitive (two- to four-fold) to both NK and LAK cell cytotoxicity. Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant interleukin-1 (alpha and beta), recombinant interferon gamma, recombinant tumor necrosis factor or combinations of the latter two failed to up-regulate tumor cell sensitivity to NK and LAK cell cytotoxicity. However, treatment with recombinant interferon gamma for 16-18 h, GM-CSF and interleukin-1 beta for 1 h induced a state of target cell resistance to both NK and LAK cell cytotoxicity. Leukoregulin may have an important physiological function in modulating NK and LAK cell cytotoxicity by increasing the sensitivity of target cells to these natural cellular immunocytotoxicity mechanisms.
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PMID:Leukoregulin up-regulation of tumor cell sensitivity to natural killer and lymphokine-activated killer cell cytotoxicity. 268 71

The role of a monocyte cytotoxic factor (CF) in monocyte-mediated lysis of leukaemia cells (K562) has been investigated using a polyclonal rabbit antiserum raised against purified CF. The CF antiserum inhibited K562 cell lysis mediated by interferon gamma (IFN-gamma)-activated monocytes. CF antiserum also inhibited monocyte-mediated lysis of antibody-coated K562 cells (AbK562). Preimmune serum at the same concentration as CF antiserum did not affect monocyte-mediated lysis, and the CF antiserum did not inhibit binding between effector and target cells, indicating that inhibition of monocyte-mediated lysis by CF antiserum was not merely a result of toxic components present in the rabbit serum, or a result of a decrease in monocyte-target cell binding. Taken together, the data suggest that CF is involved in monocyte-mediated lysis of uncoated as well as antibody-coated K562 cells.
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PMID:The role of monocyte cytotoxic factor in monocyte-mediated lysis of tumour cells. 308 37


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