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)

The effects of interferon inducers on different cytolytic mechanisms were studied in the high leukemia mouse strain AKR. A clear depression in baseline cytolytic potential and interferon-mediated stimulation of natural killer cell activities was demonstrated. This depression was most pronounced after 8 weeks of age. In contrast, antibody-dependent, cell-mediated cytotoxicity against IgG-coated chicken red blood cells was always normal. Bone marrow chimeras between CBA and AKR mice were produced to investigate the influence of bone marrow vs. host-mediated factors in these two strains with regard to interferon induction and cytolytic functions. Bone marrow genotype was found to be the dominating factor with regard to both parameters. Mice reconstituted with AKR bone marrow were deficient both in interferon production using tilorone and Newcastle disease virus as inducers, and at the level of natural killer cells responding to exogenously administered interferon. The possible relationship between these findings and the development of lymphomas in AKR mice is discussed.
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PMID:Variation of interferon induction at the bone marrow level. Studies on interferon induction in relation to natural cell-mediated cytotoxic mechanisms. 617 33

One of several human leukocyte interferon subtypes A (LeIF-A), obtained in purified form from a gene cloned in Escherichia coli, stimulated human peripheral blood natural killer cell activity, whereas another human leukocyte interferon subtype D (LeIF-D) had no effect with the use of K562 as target cells. With Daudi as target cells, both LeIF-A and LeIF-D stimulated natural killer cell activity. A hybrid human leukocyte interferon, NH2-terminal 61 amino acids and COOH-terminal 104 residues of LeIF-A and LeIF-D, respectively (LeIF-AD) showed greater stimulation than did LeIF-A, but the stimulation did not exceed that of natural buffy coat interferon. A mixture of equal antiviral units of LeIF-A and LeIF-D was no more effective than was LeIF-A alone. The cloned interferon subtypes showed differential effects on the proliferation of three human leukemic cell lines: Daudi (B-cell lymphoblastoid leukemia); BALL 1 (B-cell acute lymphoblastic leukemia); CCRF-HSB-2 (T-cell acute lymphoblastoid leukemia). Growth of Daudi cells was generally most sensitive to all the interferons tested, LeIF-A, -D, -AD, and a buffy coat preparation; no viable cells remained after 120-hr exposure to 1000-unit/ml doses of the interferons. BALL 1 was relatively resistant to the interferon subtypes tested including LeIF-AD, but this cell lines was very sensitive to a preparation of natural buffy coat interferon. CCRF-HSB-2 showed some sensitivity to all the interferons with greatest sensitivity to LeIF-A (10% of the viable cells were detected after 1000 units/ml exposure for 120 hr). In contrast to the leukemic cell lines tested, human amnion cells (WISH) and the human erythroid leukemia, K562, were resistant to the antiproliferative activity of the interferons.
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PMID:Stimulation of natural killer cell activity and inhibition of proliferation of various leukemic cells by purified human leukocyte interferon subtypes. 617 22

Natural killer cell activity was evaluated in children with acute lymphocytic and acute myelogenous leukemia. Peripheral blood mononuclear cells isolated at the time of diagnosis and before initiation of therapy were mixed with 51Cr-labeled K562 or MOLT-4 target cells at a ratio of 100:1. In 13 consecutive cases of acute lymphocytic leukemia, the mean percentage of lysis of K562 cells (15.0%) was significantly below that of adult (49.8%) and age-related controls (35.9%). A similar pattern was observed against MOLT-4 targets (acute lymphocytic leukemia, 11.3%; adults, 39.8%; and pediatric controls, 28.4%). The mean activity in 8 cases of acute myelogenous leukemia was also markedly reduced (6.8% versus K562 and 6.0% versus MOLT-4). Linear regression analyses of white blood cell, lymphocyte, and leukemia blast counts failed to demonstrate any correlation between peripheral cell counts and natural killer cell activity. Thus, it would not appear that the observed decrease in lysis was due merely to dilution of effectors with blasts. The lytic activity of cells isolated from patient blood was significantly lower than that from cells isolated from an equal volume of blood from a normal adult. These results suggest that the decreased natural killer cell activity is not explained by simple dilution. Instead, they indicate an absolute decrease in lytic potential. Additional experiments have precluded suppressor cell involvement and competitive inhibition of blasts with target cells as possible causes for depressed lysis.
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PMID:Decreased natural killer cell activity in children with untreated acute leukemia. 635 19

The NK cell associated antigens defined by the two monoclonal antibodies, HNK-1 (anti-Leu 7) and VEP13, were investigated for their mutual expression on peripheral blood lymphocytes of healthy donors. In double labelling experiments only 6 +/- 3.9% of peripheral blood lymphocytes (PBL) were found to carry both markers. When VEP13+ cells were enriched by rosette formation using VEP13 coated ox red blood cells all the NK activity was recovered in the VEP13+ cell preparation, whereas the VEP13- subset was devoid of it, despite of the fact that there was a remainder (7-13%) of HNK-1+ cells. These VEP13- HNK-1+ cells were found to also bear the T3 antigen but lack the M1 antigen. Thirty-eight to sixty-eight per cent of VEP13+ enriched cell population expressed the HNK-1 antigen too. When these cells were further separated into HNK-1+ and HNK-1- cells by means of the FACS thus yielding the VEP13+ HNK-1+ and VEP13+HNK-1- subsets, it could be demonstrated that both populations were able to mediate natural killing against K-562 target cells thus indicating existence of an HNK-1- natural killer cell population. Investigating lymphocytes from a patient suffering from a leukaemia in which 75% of cells were of LGL morphology, 32% of cells were found to be HNK-1+ while 76% of cells were shown to bear the VEP13 antigen, thus revealing a similar phenotype as observed in normal individuals. Our results indicate the existence of a HNK-1- VEP13+ natural killer cell population.
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PMID:The relationship of HNK-1 (Leu 7) and VEP13 antigens on human cells mediating natural killing. 646 85

Human leukaemia cells isolated from peripheral blood were employed as targets for natural killer (NK) cells obtained from healthy donors and the effect of pretreatment of leukaemia cells with Actinomycin D on lysability was analysed in a chromium release assay. In 8/14 leukaemia cell samples a substantial enhancement of specific release could be repeatedly obtained by exposure of leukaemia targets to Actinomycin D for 4 h. The phenomenon was seen both with interferon-treated and untreated NK cells and could be demonstrated with fresh, as well as, liquid nitrogen stored leukaemia cells. In contrast, lysis of two leukaemia cell lines could not be further enhanced and no release was seen from normal lymphocyte targets or mitogen-induced blasts. Cold target inhibition studies indicate that enhanced killing is mediated by the same kind of natural killer cell, which is active against the Molt4 and K562 leukaemia cell lines.
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PMID:Treatment of fresh human leukaemia cells with actinomycin D enhances their lysability by natural killer cells. 662 51

Two infants with recurrent infections and a history of delay in separation of the umbilical cord (1 month and 17 days) had severely impaired neutrophil mobility. In addition very poor natural killer cell (NK) activity of blood lymphocytes against a leukaemia cell line (Molt 4F) was found. Incubation of lymphocytes with lymphoblastoid interferon increased NK activity in the one case tested. No immune (gamma) interferon production was detected in Raji cell and phytohaemagglutinin (PHA) stimulated cultures from the other case. Apart from an abnormal dose-response curve in thymidine uptake after PHA stimulation of blood lymphocytes, no other abnormalities were found in a range of immunological tests. Ascorbic acid improved neutrophil mobility but had no effect, on NK activity. Both children have subsequently died from septicaemic illnesses.
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PMID:Defective immune interferon production and natural killer activity associated with poor neutrophil mobility and delayed umbilical cord separation. 681 56

Rat natural killer cell Met-ase-1 (RNK-Met-1) is a 30,000 M(r) serine protease (granzyme) found in the cytolytic granules of CD3- large granular lymphocytes (LGL) with natural killer (NK) activity. To characterize the genomic sequences responsible for the CD3- LGL-restricted expression of this gene, we screened a rat genomic library with RNK-Met-1 cDNA, and obtained bacteriophage clones that contained the RNK-Met-1 gene. The RNK-Met-1 gene comprises 5 exons and spans approximately 5.2 kilobases (kb), exhibiting a similar structural organization to a class of CTL-serine proteases with protease catalytic residues encoded near the borders of exons 2, 3, and 5. The 5'-flanking region of the RNK-Met-1 gene contains a number of putative promoter and enhancer regulatory elements and shares several regions of homology with the 5'-flanking region of the mouse perforin gene. We have prepared nested deletions from approximately 3.3 kb of the 5'-flanking region of the RNK-Met-1 gene, and inserted these upstream of the chloramphenicol acetyltransferase (CAT) reporter gene. These 5'-flanking RNK-Met-1-CAT constructs were transiently transfected into rat LGL leukemia, T-lymphoma, and basophilic leukemia cell lines. The transcriptional activity of the RNK-Met-1 5'-flanking region was strong, restricted to the RNK-16 LGL leukemia and controlled by several positive cis-acting regions spread over at least 3.3 kb. The longest and most active 5'-flanking region (-3341 to -33) was also used to drive specific expression of beta-galactosidase in RNK-16. These data are consistent with the NK cell-specific expression of RNK-Met-1 and suggest the potential utility of this gene promoter in the development of transgene models of NK cell biology in vivo.
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PMID:Cloning and characterization of a novel NK cell-specific serine protease gene and its functional 5'-flanking sequences. 760 1

Cord blood (CB) was analyzed for its alloreactive immune potential to evaluate its capacity to mediate graft vs. host disease (GVHD) and graft vs. leukemia (GVL) effects. Cord blood was observed to display minimal innate cytotoxic capacity but was capable of rapidly developing significant nonspecific natural killer cell-like effector mechanisms. Cord blood was unable to generate effective alloantigen-specific cytotoxic T lymphocytes (CTL), which was at least partially due to an altered lymphokine profile. The frequency of alloreactive T cells present in CB (whether assessed as total responding T-cell or CTL precursors) was greatly reduced as compared to adult peripheral blood lymphocytes (PBLs). However, the frequency of nonspecific effector cells was equivalent to PBLs. Significantly, CB T cells seemed to have undergone some type of developmental tolerance to maternal HLA antigens in utero, which could greatly increase the utility of CB in familial transplants. That is, CB T cells were unresponsive to noninherited maternal HLA antigens. Finally, CB demonstrated significant GVL capacity whether measured in vitro or in an animal model in vivo. Thus, the use of CB in most transplant settings should be free of the immunological problems associated with GVHD yet still be an effective mediator of GVL.
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PMID:Cord blood transplantation: implications for graft vs. host disease and graft vs. leukemia. 774 21

A 20-year-old female was admitted because of high fever, hepatosplenomegaly, severe hepatic dysfunction and coagulopathy. Peripheral blood showed pancytopenia and granular lymphocytes bearing the natural killer cell phenotype (CD2+CD3-CD16+CD56+CD57-TCR alpha beta-TCR gamma delta-) constituted 97% of leucocytes. Southern blot analysis of DNA obtained from peripheral blood mononuclear cells showed germ-line configuration of TCR beta, gamma and delta chain genes. EBV-DNA was detected in a single episomal form by using EBV-terminal repeat probe. Bone marrow findings were consistent with hemophagocytic syndrome and administration of VP-16 was effective transiently. After ten months she died from massive gastrointestinal bleeding. An in situ hybridization study identified EBV-RNA (EBER-1) in atypical lymphocytes infiltrating bone marrow, spleen and lymph nodes. Sections of liver showed steatosis and infiltration of T cells (CD3+ and EBER-1-negative) in the portal areas and few atypical lymphocytes in sinusoids. The patients developed an EBV-associated clonal proliferation of natural killer (NK) cells, but the clinical features were suggestive of chronic active EBV infection or virus-associated hemophagocytic syndrome (VAHS) rather than leukemia. Bone marrow transplantation for NK cell leukemia is an issue to be discussed.
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PMID:[Epstein-Barr virus associated natural killer cell leukemia: report of an autopsy case]. 778 57

Human T-cell leukemia virus (HTLV) is the etiologic agent of adult T-cell leukemia (ATL), a malignancy of T lymphocytes that is characterized by a long latency period after virus exposure. Intraperitoneal inoculation of severe combined immunodeficient (SCID) mice with HTLV-transformed cell lines and ATL tumor cells was employed to investigate the tumorigenic potential of HTLV type I (HTLV-I)-infected cells. In contrast to inoculation of ATL (RV-ATL) cells into SCID mice, which resulted in the formation of lymphomas, inoculation of HTLV-I- and HTLV-II-transformed cell lines (SLB-I and JLB-II cells, respectively) did not result in tumor formation. Immunosuppression of SCID mice, either by whole-body irradiation or by treatment with an antiserum, anti-asialo GM1 (alpha-AGM1), which transiently abrogates natural killer cell activity in vivo, was necessary to establish the growth of tumors derived from HTLV-transformed cell lines. PCR and flow cytometric studies reveal that HTLV-I-transformed cells are eliminated from the peritoneal cavities of inoculated mice by 3 days postinoculation; in contrast, RV-ATL cells persist and are detected until the mice succumb to lymphoma development. The differing behaviors of HTLV-infected cell lines and ATL tumor cells in SCID mice suggest that ATL cells have a higher tumorigenic potential in vivo than do HTLV-infected cell lines because of their ability to evade natural killer cell-mediated cytolysis.
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PMID:Potential role of natural killer cells in controlling tumorigenesis by human T-cell leukemia viruses. 781 16


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