Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation antigens expressed by activated B cells, but not by resting B cells, are excellent candidate molecules for lymphokine receptors, which are expressed after B cell activation. HC2 is a previously described hairy cell leukemia associated antigen, which is not expressed by chronic lymphocytic leukemia B cells. HC2 is also found on activated B cells but not on resting B cells. Here we demonstrate that HC2 is not a B lineage restricted antigen and may be expressed by other activated cell types. Antibody to HC2 inhibits the activity of partially purified B cell growth factor in two different assays and inhibits B cell differentiation induced by pokeweed mitogen or Staphylococcus aureus Cowan stain I with interleukin-2. The HC2 antigen may therefore have a distinct role in normal B cell differentiation.
Leukemia 1987 Apr
PMID:A hairy cell leukemia associated antigen (HC2) has a distinct role in normal B cell differentiation. 349 44

Hairy cell leukemia cell lines were established from eight untreated patients using purified B cell growth factor (BCGF) in vitro. These cell lines maintained their original cell surface immunophenotype for about 1 month, after which they began to lose one or more of their characteristic surface antigens. The cell lines also maintained typical hairy cell leukemia morphology for 2-3 months in vitro but later showed an increasing number of multinucleate giant cells that maintained a B cell surface phenotype. The cell lines became independent of exogenously provided BCGF after at least 1 month in vitro and secreted BCGF activity into culture supernatants in most cases. Some cell lines also acquired Epstein-Barr virus nuclear antigen positivity after variable period. Two hairy cell leukemia patients also showed hyperactive T cell responses in vitro and exhibited spontaneous T cell proliferation in culture without exogenously supplied interleukin-2. These T cell lines had the T helper phenotype and secreted significant amounts of T cell-associated lymphokines with BCGF and interleukin-2 activity into culture supernatants.
Leukemia 1987 Apr
PMID:In vitro studies on leukemia cells and T lymphocytes in hairy cell leukemia. 349 45

The fusion toxin DAB389IL-2 is composed of the catalytic (C) and transmembrane (T) domains of native diphtheria toxin to which human interleukin-2 (IL-2) has been genetically fused (1,2). Following binding to the IL-2 receptor, the fusion toxin is internalized by receptor mediated endocytosis, and upon acidification of the endocytic vesicle, the T domain spontaneously inserts into the membrane, and facilitates the delivery of the C domain to the cytosol (3,4). In order to further study the process by which the C domain is delivered to the target cell cytosol, we genetically fused an eleven amino acid epitope derived from the vesicular stomatitis virus (VSV) G protein to the N-terminal end of DAB389IL-2. The epitope labelled fusion toxin, VSV-G-DAB389IL-2, was found to retain IL-2 receptor specific binding and cytotoxic activity. Target cells were incubated for various times in the presence of VSV-G-DAB389, fixed and then treated with anti-VSV G and FITC conjugated secondary antibody. Laser scanning confocal microscopy was used to determine the location of the fluorescent signal. The VSV-G epitope tagged fusion toxin was found only to be associated with small vesicles that were situated adjacent to the plasma membrane. These results suggest that the C domain of the fusion toxin is associated with an early intracellular compartment and is rapidly delivered to the cytosol. Since channel formation by the T domain is necessary for the delivery of the C domain, it follows that T domain insertion into the membrane also occurs early in the intoxication pathway.
Leukemia 1994 Apr
PMID:Epitope tagging of DAB389IL-2: new insights into C-domain delivery to the cytosol of target cells. 751 76

The aims of this study were to investigate the role of cytokines (tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) and interleukin-2 (IL-2) in augmenting graft-versus-leukaemia (GVL). We have investigated the effector cells involved in GVL, by studying the role of these cells in purging of the cell line K562 in short-term bone marrow cultures. The effect of the addition in vitro of rGCSF was also studied. Monitoring of purging was achieved by cytotoxicity assays, DNA analysis and the use of the polymerase chain reaction for the detection of bcr/abl transcripts in the Philadelphia positive (Ph+) K562 cell line. Supernatants from IL-2-treated and non-treated bone marrow were tested for cytokine production (TNF alpha and IFN gamma). The results have shown that the main cytotoxic effector cells in the bone marrow generated by IL-2 have the CD56+ CD8+ phenotype. Overnight incubation of bone marrow was sufficient to generate cytotoxic cells as measured by Chromium51 (Cr51) release assays. Measurable levels of TNF alpha but not IFN gamma were also detected in supernatants. Addition of TNF alpha and IFN gamma to the IL-2 in the bone marrow cultures augmented the cytotoxicity but tended to inhibit progenitor cell growth as measured by granulocyte-macrophage colony-forming unit (GM-CFU) and erythroid blast-forming unit (BFU-e) assays. An estimate of the purging of the marrow could also be achieved by DNA analysis of K562 DNA in bone marrow. The bcr/abl transcript could still be detected by PCR analysis in marrow containing 1% K562 and treated with IL-2 for 24 h, but by 6 days of incubation the bcr/abl transcript was weak or undectable. The results suggest that although reduction in the proportion of leukaemia in contaminated marrow can be detected after incubation with IL-2 for 24 h, complete elimination of minimal residual disease requires longer incubation times.
Leukemia 1995 Mar
PMID:Cytokine treatment of human bone marrow activates anti-leukaemia effector cells: monitoring of purging by polymerase chain reaction and DNA analysis. 753 66

Acute myeloid leukemia (AML) cells express the surface adhesion proteins intercellular adhesion molecule-1 (ICAM-1, CD54) and lymphocyte function associated molecule-3 (LFA-3, CD58). Exposure to the myeloid growth-promoting cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulates expression of ICAM-1 and LFA-3 on AML cells but does not increase their sensitivity to lysis by interleukin-2-activated natural killer cells (LAK) in 51Cr assays. However when AML cells are exposed to GM-CSF prior to incubation with LAK, their subsequent clonogenic activity is significantly reduced. If a blocking antibody to ICAM-1 is added during the incubation period of AML with LAK, the inhibitory effect is completely ablated. A less pronounced effect is observed with an antibody to LFA-3. ICAM-1 is expressed on a greater proportion of CD34+ than CD34- AML cells and exposure to GM-CSF induces a significantly greater upregulation of ICAM-1 on leukemic CD34+ cells than their CD34- counterparts. These data suggest that the inhibitory effect of IL-2-activated natural killer cells on clonogenic AML cells is mediated principally via the lymphocyte function associated molecule-1 (LFA-1)/ICAM-1 interaction. Interleukin-2 upregulates LFA-1 expression on natural killer cells. Simultaneous administration of effector cell activators such as IL-2 and target cell modulators such as GM-CSF may have a therapeutic benefit in patients with minimal residual myeloid leukemia.
Leukemia 1995 Apr
PMID:GM-CSF enhances IL-2-activated natural killer cell lysis of clonogenic AML cells by upregulating target cell expression of ICAM-1. 772 3

The immune response to a murine myeloid leukemia (cell line C1498) was studied in vitro and in vivo. Natural killer (NK) cells and CD8+ cytotoxic T lymphocytes (CTL) were shown to lyse C1498 in vitro through the binding of leukocyte function antigen-1 (LFA-1) on effectors and intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on C1498 target cells. However, the ability of nonimmunized mice to resist an in vivo challenge of a low dose (10(4)) of C1498 was NK-cell, but not T-cell dependent. The failure of T cells to participate in the immune surveillance of a low leukemia burden appeared, in part, because of a lack of expansion of leukemia reactive CTL precursors (CTLp). Leukemia reactive CTLp frequency estimations in naive and leukemia bearing mice were not significantly different (range, 1:20,600 to 1:74,000) in contrast to immunized mice (range, 1:1,400 to 1:4,400). Leukemia reactive CTLp could be expanded to a level that could apparently mediate in vivo immune surveillance of 10(5) leukemia cells by injection of irradiated leukemia cells intraperitoneally (IP) or subcutaneously (SC), but not intravenously (IV). However, IV injection of 10(5) live leukemia cells engineered to secrete interleukin-2 (IL-2) resulted in systemic immunity mediated primarily by CD8+ T cells. We conclude that NK cells can mediate immune surveillance of a low leukemia burden. CD8+ CTL-mediated immune surveillance can eliminate a higher leukemia burden than NK cells, but requires T-cell help, which can be delivered by local IL-2. Both NK and CTL-mediated immune surveillance of C1498 murine myeloid leukemia is dependent on recognition through the LFA-1:ICAM adhesion pathway.
 ...
PMID:Dependency on intercellular adhesion molecule recognition and local interleukin-2 provision in generation of an in vivo CD8+ T-cell immune response to murine myeloid leukemia. 772 79

Cell lines of myeloid origin have been shown to express interleukin-2 receptors (IL-2R). Here, we demonstrate the expression of IL-2R alpha and IL-R beta on the CML blast cell line K562 by FACS analysis and cross-linking assay. Furthermore, we examined the effect of IL-2 on leukemic progenitor growth, employing K562 as a model. Clonogenic growth was assessed after 3 days of culture by colony formation in a serum-free, semi-solid assay system. IL-2 was found to exhibit a dose-dependent suppressive effect on K562 clonogenicity with 48% inhibition of colony formation at 250 U IL-2 and 60% inhibition at 1000 U IL-2. Philadelphia chromosome (Ph)-positive K562 cells possess multiple copies of the bcr/abl fusion gene whose transcript and protein product (p210) is thought to confer growth advantage to CML cells. We therefore investigated IL-2-dependent modulation of bcr/abl mRNA accumulation and p210 protein levels in K562 cells. After 4 h of culture in the presence of IL-2, a 3-15-fold reduction of bcr/abl mRNA accumulation was demonstrated by competitive reverse PCR. Reduction of bcr/abl fusion protein levels was demonstrated at 24 h of IL-2-supplemented cell culture, employing p210 recognizing monoclonal antibodies (mAbs) in FACS analysis. Levels of proliferation marker Ki67 were only marginally affected. We conclude: (1) K562 cells express both IL-2R alpha and IL-R beta; (2) IL-2 inhibits clonogenic growth of K562 in a dose-dependent manner; and (3) IL-2-mediated inhibition of K562 proliferation is preceded by a reduction of bcr/abl mRNA accumulation and p210 protein levels.
Leukemia 1995 Mar
PMID:IL-2 inhibits proliferation of K562 cells and reduces accumulation of bcr/abl mRNA and oncoprotein. 788 40

A new NK cell line, designated as TKS-1, was established from the peripheral blood of a patient with large granular lymphocyte (LGL) leukemia which showed highly aggressive clinical course. The original leukemic cells, which had a surface phenotype of CD2+, CD3-, CD16-, and CD56+, proliferated well in the presence of 200 U/ml of interleukin-2 (IL-2). Morphologically, TKS-1 cells had immature nuclei and abundant cytoplasm with fine azulophilic granules. Surface phenotype of the cell line was CD2+, CD3-, CD16-, CD57-, and CD56-, CD56 antigen disappearing during the culture. Analyses of T-cell receptor (TCR) beta- and gamma-chain genes showed germ line configurations. Functionally, TKS-1 cells showed significant cytotoxicity against K562, Raji, and Daudi target cells. We consider that TKS-1 cells originated from CD16-negative immature type of peripheral blood NK cells. This cell line will be useful not only for the investigation of NK cell leukemia, but also for that of the mechanism of cytotoxicity mediated by normal NK cells.
Leukemia 1994 Nov
PMID:Establishment of a new natural killer (NK) cell line, TKS-1, from a patient with aggressive type of large granular lymphocyte (LGL) leukemia. 796 45

High-dose recombinant human Interleukin-2 was given to 21 patients with acute myeloid (n = 11) or lymphoid (n = 10) leukemia in relapse. A rapid decrease in the peripheral leukemic blasts numbers was observed in six patients. We were unable to demonstrate at the bone marrow level a diminution in the percentage of leukemic blasts. However an increase in the expression of the adhesion molecule CD54/ICAM-1(LFA-1 ligand) affected the leukemic bone marrow blasts of these six patients. This increase in CD54 was found in eight of the 11 (73%) AML and four out of the ten (40%) ALL blasts and CD58/LFA-3 (CD2 ligand) to a lesser extent. This increased expression was not associated with modifications in the expression of MHC class II molecules. In vivo IL-2 also dramatically modified the bone marrow T-cell subsets via the increase of CD3+ cells expressing the CD45RO 'memory' marker (six out of the eight tested patients) or CD54 (seven out of the eight tested patients). Altogether these results demonstrate that leukemic blasts can be affected by in vivo IL-2 via mechanisms that could involve T cells.
Leukemia 1994 Jul
PMID:Modifications of leukemic blast cells induced by in vivo high-dose recombinant interleukin-2. 803 17

An Epstein-Barr virus (EBV) genome-positive T-cell line, designated EBT-8, was established from peripheral blood of a patient with EBV genome-positive large granular lymphocyte leukemia of T-cell origin. The cells have been cultured continuously in RPMI-1640 medium supplemented with 10% fetal calf serum and 40 U/ml interleukin-2 for more than 18 months. Analysis of T-cell receptor gene rearrangement demonstrated similar rearrangement between the fresh leukemic cells and EBT-8 cell line. The cell line has several azurophilic granules in its cytoplasm and activated cytotoxic/suppressor T-cell surface antigens (CD2, CD3, CD8, HLA-DR and T-cell receptor alpha/beta). Karyotypic analysis of the cell line showed several chromosomal abnormalities. EBV DNA was demonstrated in the cells by Southern blot hybridization and about five copies of covalently closed circular DNA per cell were detected by Gardella gel analysis. Clonotypic episomal EBV DNA was observed in the cells by Southern blot hybridization with EBV-terminal fragment probe. EBV-encoded small RNA, EBER1 were demonstrated in all cells by in situ hybridization. EBV-encoded proteins, EBNA and LMP1 were demonstrated by immunofluorescence technique. EBV activation was observed after 12-O-tetradecanoylphorbol-13- acetate treatment of the cells. These results demonstrated the establishment of a T-cell line with latent EBV genomes and suggested the involvement of EBV to the large granular lymphocyte leukemia of T cells.
Leukemia 1994 Aug
PMID:Establishment and characterization of the T-cell line, EBT-8 latently infected with Epstein-Barr virus from large granular lymphocyte leukemia. 805 83


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