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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3. Cytotoxicity of peripheral blood mononuclear cells at an effector: target (E:T) cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To establish the line, cells from the peripheral blood were placed into enriched alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10(-4) M beta-mercaptoethanol and 10(-6) M hydrocortisone. Growth of the line (termed NK-92) is dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is sufficient to maintain proliferation. Conversely, cells die within 72 h when deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7 induces short-term proliferation measured by 3H-thymidine incorporation. None of the other cytokines tested (IL-1 alpha, IL-6, TNF-alpha, IFN-alpha, IFN-gamma) supported growth of NK-92 cells which have the following characteristics: surface marker positive for CD2, CD7, CD11a, CD28, CD45, CD54, CD56bright; surface marker negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34, HLA-DR. DNA analysis showed germline configuration for T-cell receptor beta and gamma genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2 concentration. The p75 IL-2 receptor is expressed on about half of the cells at low density irrespective of the IL-2 concentration. NK-92 cells kill both K562 and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86% respectively, at an E:T cell ratio of 5:1). The cell line described here thus displays characteristics of activated NK-cells and could be a valuable tool to study their biology.
Leukemia 1994 Apr
PMID:Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. 815 60

Adoptive immunotherapy is used to treat malignant tumors resistant to conventional therapeutic modalities. Patients with metastatic melanoma, renal cell carcinoma or mesothelioma are most likely to benefit from this treatment. Tumor infiltrating lymphocytes (TIL) contain tumor specific killer cells and are found to be the most effective. When TIL is not available or until it can be produced in sufficient amount, autologous activated lymphocytes (AAL) are an alternative. AAL are leukapheresed lymphocytes, activated by conditioned medium from OKT3 stimulated autologous lymphocytes. Subcutaneous IL-2 and oral cimetidine are also administered to support the reinfused AAL and to inhibit activation of CD8+ suppressor cells, respectively. To improve the yield and activation of reinfused lymphocytes, addition of IL-2 to the culture medium was tested in different time intervals after the onset of the culture. Interleukin-2 added in the first or second day i) improved the yield of activated lymphocytes; ii) increased the expression of activation markers CD25 (IL-2 receptor) and HLA-DR and iii) augmented killing of tumor cells. Later addition of IL-2 had no or negative effects. In vitro priming of peripheral blood mononuclear cells with autologous or allogeneic but histologically identical tumors was used to increase tumor-specificity of AAL. Autologous serum, containing antibodies specific to tumor cells, facilitated antigen presentation and yielded cytotoxic lymphocytes capable of efficiently killing tumor cells.
Leukemia 1994 Apr
PMID:Adoptive immunotherapy with activated peripheral blood lymphocytes. 815 78

The signal transduction mechanism of the interleukin-2 receptor (IL-2R) remains largely undefined. The cytosolic domain of the IL-2R beta subunit is known to be essential for coupling to intracellular signaling pathways such as protein tyrosine kinase (PTK) and for control of IL-2 dependent cellular proliferation. A panel of cell lines that express IL-2R beta chains that contain sequential truncation mutations within the cytosolic domain were constructed. These cell lines were used to map the interaction of IL-2R with PTK activation, and the linkage of PTK function to activation of the enzyme phosphatidylinositol-3-kinase (Pl3K). The data show that the amino terminal segment of the acidic region (residues 314-350) within IL-2R beta is a critical site for PTK activation, and that activation of Pl3K is linked to IL-2 dependent tyrosine phosphorylation.
Leukemia 1994 Apr
PMID:The membrane proximal segment of the IL-2 receptor beta-chain acidic region is essential for IL2-dependent protein tyrosine kinase activation. 815 89

Recent evidence of cell membrane expression of interleukin-2 receptors (IL-2R) by malignant B cells in hairy cell leukemia (HCL) and B-chronic lymphocytic leukemia (B-CLL) has lead to speculation that growth factors, such as IL-2, may play a role in the pathophysiology of these diseases. However, to date, it is not clear that IL-2 is a consistent growth factor in vitro or in vivo for malignant B cells. What then is the potential significance of membrane IL-2R on the malignant B-cell membrane? Laboratory analysis indicates that the malignant cells are the source of elevated serum levels of soluble Tac protein (sIL-2r alpha) in both diseases. Indeed, these cells spontaneously secrete sIL-2R alpha into culture medium. We speculate that the presence of an expanding mass of malignant B cells possessing high and low affinity membrane IL-2R may contribute significantly to the associated immunodeficiency seen in B-CLL. In particular, it is the cell associated high affinity IL-2R that have the greatest potential for reducing the levels of free IL-2 available to normal immune cells.
Leukemia 1994 Jan
PMID:Does IL-2 receptor expression and secretion in chronic B-cell leukemia have a role in down-regulation of the immune system? 828 5

We previously demonstrated that mature T lymphocytes responding to either IL-2 or IL-4 undergo apoptosis upon T cell antigen receptor stimulation, and have termed this potential negative feedback pathway propriocidal regulation. Using cell cycle inhibitors, we now show that T cell growth lymphokines cause the entry of T cells into vulnerable stages of the cell cycle in which T cell receptor occupancy causes apoptosis.
Leukemia 1993 Aug
PMID:Ligand-induced apoptosis of mature T lymphocytes (propriocidal regulation) occurs at distinct stages of the cell cycle. 836 Dec 32

The properties of human CD45RA and CD45R0 T cells are described. CD45R0 cells respond to recall antigens and provide help for B lymphocytes. They produce a wide variety of cytokines including IL-2, IL-4 and IFN-gamma. CD45RA T cells respond poorly to recall antigens and produce mainly IL-2. The phenotype of CD45R0 cells suggests that they may be in cycle and in vivo data shows that they have a short lifespan while CD45RA cells are long lived. The lineage relationship of the two subsets is not clear but in vivo and in vitro evidence suggests bidirectional conversion between CD45RA and CD45R0 phenotypes.
Leukemia 1993 Aug
PMID:Memory and the lifespan of human T lymphocytes. 836 Dec 33

We have shown that therapy of AML patients in second remission with continuous infusion of IL-2 resulted in generation of cytotoxic lymphocytes in peripheral blood and bone marrow. However, these lymphocytes mediated cytotoxicity only against tumor cell lines, and not against AML blasts. Additional in vitro activation with higher dose of IL-2 was necessary for induction of AML blast oncolysis. This indicates that the concomitant treatment with continuous and periodic bolus IL-2 infusion may be necessary, to achieve higher levels of IL-2 and subsequently, more potent lymphocyte activation. Alternatively, it may not be possible to induce optimal antileukemia response in vivo with tolerable doses of IL-2, and the adoptive therapy with in vitro supremely activated lymphocytes may represent an option. In this article, we discuss several approaches to the supreme activation of cytotoxic lymphocytes against highly resistant AML blasts and their possibilities in leukemia therapy.
Leukemia 1993 Aug
PMID:Recent approaches to induction of cytotoxic lymphocytes against leukemia. 836 Dec 37

In the present study, we have investigated the leukemic cells obtained from 16 patients with acute myeloid leukemia (AML) at diagnosis for the membrane expression of p55 (alpha) and p75 (beta) interleukin-2 receptor (IL-2R) chains using specific monoclonal antibodies (mAbs), as well as for the presence of their transcripts using Northern blot analysis. In addition, immunoprecipitation of the p75 membrane molecule with TU27 and Mik-beta 1 mAbs was carried out in selected cases. The p75 IL-2R beta transcripts were detected in all cases, whereas the membrane p75 molecule was demonstrable by flow cytometry in three cases. However, data from the immunoprecipitation analysis suggest that the lack of the p75 IL-2R detection by flow cytometry might be caused by the low density of molecules per cell rather than the fact that the specific mRNA is not translated into the p75 surface molecule. In addition, a consistent membrane positivity with an anti-p55/CD25 mAb, present on fresh uncultured blasts in 37.5% of the cases, became detectable after short-term culture in 75% of cases. In each individual case, a strict correlation was found between membrane CD25 reactivity and the expression of p55 mRNA. Taken together, our data suggest that the expression of both alpha (p55) and beta (p75) IL-2R molecules is a common feature of leukemic cells in AML, and provide new arguments for reassessing the possible role of IL-2 in leukemic growth.
Leukemia 1993 Mar
PMID:Alpha (p55) and beta (p75) chains of the interleukin-2 receptor are expressed by AML blasts. 844 47

In in vivo allogeneic bone marrow transplantation studies with the Brown Norway (BN) rat as recipient and the WAG/Rij rat as allogeneic donor a significant graft-versus-leukemia (GVL) effect is observed. Studies were performed to investigate whether lymphokine-activated killer (LAK) cells play a role in this GVL effect. Splenocytes from WAG/Rij and BN rats were activated in vitro by recombinant human interleukin-2 (rhIL-2) for 5-6 days. The cytolytic activity of these LAK cells was tested on four rat solid tumor cell lines, i.e. an ureter carcinoma, a rhabdomyosarcoma, and two lung tumors, and on leukemic cells derived from the BN rat acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia (L4415). The panel of target cells also included the murine cell lines P815 and YAC. Both WAG/Rij and BN LAK cells were not capable of lysing the leukemic cells in contrast to significant cytolytic activity on the rat solid tumor cell lines and P815 and YAC. BNML cells showed to be resistant to lysis by human NK cells. Phenotypical analysis of the rat LAK population revealed a decrease in the CD4/CD8 ratio compared to the unstimulated splenocyte population. Rat LAK cells displayed no antibody-dependent cellular cytotoxicity (ADCC) on the leukemic cells, whereas IL-2-stimulated human peripheral blood cells showed moderate ADCC activity on the leukemic cells. To investigate whether cytokines play a role in lysis of leukemic target cells, graded numbers of LAK cells and leukemic cells were co-cultivated for seven days in an agar-based colony culture system. This resulted in moderate suppression of leukemic colony formation. From the current in vitro studies it appears that the graft-versus-leukemia observed in in vivo allogeneic bone marrow transplantation studies is probably not due to a direct leukemic cell kill by LAK cells.
Leukemia 1993 May
PMID:In vitro resistance of the brown Norway rat acute myelocytic leukemia (BNML) to lymphokine-activated killer activity. 848 27

Human T cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T cell leukemia (ATL) transforms human T cells in vitro and in vivo. Tax, the major transactivator of HTLV-I is critical for the initial events involved in transformation, however, the later steps required for progression from an IL-2 dependent state to one of IL-2 independence remain to be clarified. We investigated the potential role of p53 protein in this process employing several IL-2 dependent and independent HTLV-I transformed cell lines. All cell lines examined were found to be wild-type in the p53 coding region usually associated with inactivating mutations using RT-PCR-SSCP analysis and DNA sequencing. Levels of p53 protein were consistently higher in IL-2 independent lines compared to IL-2 dependent ones. Lack of functional p53 activity was observed only in IL-2 independent cell lines using a transfection assay with a B-galactosidase reporter gene construct responsive to wild-type p53 protein. Increased steady state levels of wild-type p53 protein associated with its functional inactivation appear to be linked to the loss of IL-2 dependent growth in HTLV-I transformed lymphocytes.
Leukemia 1995 Dec
PMID:Functional inactivation of wild-type p53 protein correlates with loss of IL-2 dependence in HTLV-I transformed human T lymphocytes. 860 20


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