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)

A 28-year-old male was admitted to our hospital because of hepatosplenomegaly and granular lymphocytosis. His peripheral leukocyte count was 3,000/microliters with 43% of granular lymphocytes (GL). These GLs were immunologically phenotyped as CD2+CD3-CD4-CD8-CD16+CD56+HLA-DR+ and were found that TcR genes coding beta and gamma chains were not rearranged. Chromosomal analysis of his GLs stimulated with IL-2 showed 47 XY, +8. This patient was diagnosed as a granular lymphocyte leukemia of natural killer cell type. Blood chemistry showed elevation of serum GOT, GPT and LDH values. The fever persisted until administration of prednisolone was initiated. But 40 days after, high fever appeared again and the liver and spleen were extremely enlarged. Combined chemotherapy was then started but resulted in no effects. He died of hepatic failure on the 77th day from admission. 47 XY, +8, that has been reported in acute non-lymphocytic leukemia and myelodysplastic syndrome, may be related to the pathogenesis in some cases of granular lymphocyte leukemia.
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PMID:[Granular lymphocyte leukemia of natural killer cell type; association with 47 XY, +8 by interleukin 2 (IL-2)-stimulated chromosomal analysis]. 225 62

We have isolated a subline of the M-07 human megakaryoblastic leukemia cell line, designated M-07e, that requires either interleukin-3 (IL-3) or granulocyte macrophage colony-stimulating factor (GM-CSF) for growth, even in the presence of fetal calf serum. This cell line will not grow long term in any other cytokine although it responds slightly to IL-2, IL-4, IL-6, IL-9, and interferon-gamma. We have used the M-07e subline to develop a quantitative bioassay for the measurement of levels of either GM-CSF or IL-3. This assay is as sensitive to either factor as the human bone marrow colony assay (CFU-GM) or the chronic myelogeneous leukemic (CML) blast cell proliferation assay for these factors and is much more convenient and reliable than either. With this assay, as little as 25-50 pg/ml of either IL-3 or GM-CSF can be detected, a level that should render the assay useful for analysis of these molecules in samples from patients undergoing colony-stimulating factor therapy and from conditioned media from natural sources of the factors. In these cases, neutralizing antisera to each cytokine are required to demonstrate the specificity of the assay. This assay, in combination with quantitative immunoassays, should greatly facilitate the analysis of the roles of IL-3 and GM-CSF in regulating hematopoiesis both in patients and in natural sources of the cytokines.
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PMID:M-07e human leukemic factor-dependent cell line provides a rapid and sensitive bioassay for the human cytokines GM-CSF and IL-3. 227 55

The aporphine alkaloids, dicentrine, glaucine, corydine, and apomorphine were shown to have inhibitory activity against several mouse tumor cell lines, leukemia P388 and L1210, melanoma B16, bladder cancer MBC2, and colon cancer Colon 26 in culture. These aporphine alkaloids also inhibited the mitogen-induced lymphocyte proliferation as well as the growth of IL-2 dependent CTLL2 line in a dose-dependent way. Of the four alkaloids apomorphine proved to be most potent in the inhibitory action. Apomorphine treatment resulted in some prolongation of survival time of the mice inoculated i.p. with P388, although its activity was not enough to meet the standard criterion for antitumor activity.
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PMID:Suppression of tumor cell growth and mitogen response by aporphine alkaloids, dicentrine, glaucine, corydine, and apomorphine. 229 Jan 26

We describe a new, spontaneously occurring BALB/c-derived murine T-cell leukemia. The leukemic cells, designated LB, grow rapidly and progressively in the syngeneic host with no signs of effective immunological resistance. LB cells expressed the Thy-1+, Lyt-2+, L3T4-, CD3- class-I+, CD25+ (IL-2 receptor, IL-2R), class-II-, gp70- phenotype. As LB cells express IL-2, as indicated by staining with 2 distinct anti-CD25 IL-2R monoclonal antibodies (MAbs), the therapeutic efficacy of IL-2-diphtheria toxin-related protein was tested on this leukemic model. IL-2-diphtheria toxin, but not diphtheria toxin, efficiently inhibited the proliferation of LB cells. The proliferation of a murine myeloma cell line, which does not express IL-2R, was not inhibited by IL-2-diphtheria toxin. The possible implantation of this animal model in fundamental and practical studies is discussed.
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PMID:Murine spontaneous T-cell leukemia constitutively expressing IL-2 receptor--a model for human T-cell malignancies expressing IL-2 receptor. 229

The in vitro incubation of NK cells with the lymphokine IL-2 stimulates the development of a population of activated cytotoxic lymphocytes (LAK cells). These activated cells have the capacity to recognize and kill a wide range of neoplastic cells. The cytotoxic activity of LAK cells does not appear to be directed against normal, non-neoplastic cells and we have recently examined the potential for using LAK cells as a method of purging bone marrow for autologous transplantation in patients with widespread neoplastic diseases. We have utilized an experimental system consisting of the incubation of LAK cells from inbred F344 rats and normal bone marrow and demonstrated that this procedure does not interfere with the ability of the treated bone marrow to reconstitute lethally-conditioned recipients. The frequency and rate of reconstitution is the same in treatment and control groups, including incubation periods that extend up to 18 hours. When RNK-16 leukemia cell line (a spontaneous large granular lymphocyte leukemia that is syngeneic to the F344 strain) is added to the incubation mixture, the LAK cells have the ability in vitro to recognize the neoplastic cells and prevent the transmission of the leukemia to naive animals following bone marrow transplantation. As expected from the in vitro LAK cytotoxic activity, these activated cells are capable of recognizing and eliminating a variety of neoplasms. To date we have tested three different hematopoietic tumor lines derived from the F344 strain and one that was induced in an unrelated BN strain. In each case, the F344 LAK cells demonstrated an ability to prevent the transmission of a fatal leukemia and significantly prolong the survival of animals that had received larger numbers of neoplastic cells. The tumor lines examined included the RNK-16 line (NK cells), the Dunning leukemia (monocyte-lymphoblastic leukemia), a T-lymphocyte lymphoma and the acute myelogenous leukemia of BN rats (BN AML). Comparison of the results of these purging experiments to those seen when control animals are injected with graded doses of the individual tumors indicate that the LAK cells are eliminating approximately 2-3 logs of neoplastic cells. The ability of LAK cells to kill a wide range of tumors without damage to the ability of the recipient stem cells to reconstitute the bone marrow may allow for an important application for this type of purging technique in patients with neoplasms for which specific immunological or chemical therapies do not exist.
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PMID:Lymphokine-activated killer (LAK) cell purging of bone marrow. 230 77

The aim of the current study was to determine whether cultured tumor Ag-specific T cells could be induced to grow and maintained functional in large numbers in vivo by intermittent restimulation in vivo with specific Ag plus IL-2. T cells derived from spleens of B6 mice (Thy-1.2) immune to FBL-3, a Friend virus-induced leukemia, were activated by in vitro stimulation with irradiated FBL-3 and expanded by culture for 14 days with low concentrations of IL-2. The resultant FBL-3-specific T cell lines were adoptively transferred into cyclophosphamide pretreated congenic hosts (B6/Thy-1.1), and restimulated every 14 days by an injection of irradiated FBL-3 plus a 7-day course of IL-2. Donor T cells residing in the host were identified and quantified by use of antibody to the Thy-1.2 allele. The results confirmed that stimulation with FBL-3 on the day of transfer (day 0) plus IL-2 on days 0 to 6 induced rapid growth of donor T cells to approximately an 11-fold increase in total donor T cell number recoverable from host ascites and spleen by day 7. However, prolonging the course of IL-2 administration to 35 days did not maintain the number or the specific cytolytic function of donor T cells. By contrast, intermittent restimulation with specific Ag plus IL-2 induced intermittent regrowth of donor T cells in vivo, maintained the number of donor T cells in vivo at greater than the number input for longer than 1 mo, and allowed detection of substantially augmented donor T cell-mediated specific antitumor function over that period of time.
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PMID:Adoptively transferred antigen-specific T cells can be grown and maintained in large numbers in vivo for extended periods of time by intermittent restimulation with specific antigen plus IL-2. 233 28

We analyzed the expression of the interleukin-2 receptor (IL-2R) beta chain (p70-75) on various leukemic cells from 44 patients by flow cytometric analysis using the IL-2R beta chain-specific monoclonal antibody (MoAb), designated Mik-beta 1, which has been recently developed. Flow cytometric analysis demonstrated the expression of the IL-2R beta chain on granular lymphocytes (GLs) from all eight patients with granular lymphocyte proliferative disorders (GLPDs), on adult T-cell leukemia (ATL) cells from all three patients with ATL, and on T-cell acute lymphoblastic leukemia (T-ALL) cells from one of three patients with T-ALL. Although GLs from all the GLPD patients expressed the IL-2R beta chain alone and not the IL-2R alpha chain (Tac-antigen: p55), ATL and T-ALL cells expressing the beta chain coexpressed the alpha chain. In two of seven patients with common ALL (cALL) and in both patients with B-cell chronic lymphocytic leukemia, the leukemic cells expressed the alpha chain alone. Neither the alpha chain nor the beta chain was expressed on leukemic cells from the remaining 28 patients, including all 18 patients with acute nonlymphocytic leukemia, five of seven patients with cALL, all three patients with multiple myeloma, and two of three patients with T-ALL. These results indicate that three different forms of IL-2R chain expression exist on leukemic cells: the alpha chain alone; the beta chain alone; and both the alpha and beta chains. To examine whether the results obtained by flow cytometric analysis actually reflect functional aspects of the expressed IL-2Rs, we studied the specific binding of 125I-labeled IL-2 (125I-IL-2) to leukemic cells in 18 of the 44 patients. In addition, we performed 125I-IL-2 crosslinking studies in seven patients. The results of IL-2R expression of both 125I-IL-2 binding assay and crosslinking studies were in agreement with those obtained by flow cytometric analysis. These results indicate that flow cytometric analysis using MoAbs, anti-Tac, and Mik-beta 1 is useful for detecting the expression of the IL-2R chains.
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PMID:Flow cytometric analysis of expression of interleukin-2 receptor beta chain (p70-75) on various leukemic cells. 238 56

We have previously reported that lck mRNA (a lymphocyte-specific protein tyrosine kinase gene) is absent in human T-cell leukemia virus type I (HTLV-I)-infected interleukin-2(IL-2)-independent T-cell lines, while HTLV-I-negative T-cell lines and HTLV-I-positive IL-2-dependent ones express a large amount of lck mRNA. To further investigate the levels of lck expression, we prepared rabbit anti-Lck antiserum directed against the synthetic oligopeptide of 32 amino acids corresponding to the carboxy terminus of this gene product, p56lck. Using this antiserum, we show that HTLV-I-positive T-cell lines, whether they are IL-2-dependent or not, scarcely express p56lck. In other words, IL-2-dependent HTLV-I-positive T-cell lines seldom produce p56lck in spite of high expression of lck mRNA. Absence of p56lck is suspected of playing an important role in malignant transformation of HTLV-I-infected T-cells.
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PMID:Human T-cell leukemia virus type-I-infected T-cell lines scarcely produce p56lck, whether or not they express lck mRNA. 238 77

T cells from allogeneic bone marrow grafts are responsible for a graft versus leukemia effect. Use of recombinant Interleukin-2 (rIL-2) after autologous bone marrow transplantation (BMT) may enhance immune function and hopefully reproduce the allogeneic reaction. We report here the hematologic and immunologic changes observed in the first 10 patients of a phase 1 trial studying the infusion of IL-2 after autologous BMT. All patients had high-risk malignancies and received 6 days of a constant infusion of IL-2 (Eurocetus, Amsterdam, The Netherlands) at dose of 3 x 10(6) Cetus Units/m2/d, 79 +/- 12 days after autologous BMT. Clinical toxicities involving cutaneous, cholestatic, gastrointestinal, and hemodynamic effects occurred during IL-2 treatment but reversed in all cases. Completion of treatment was 91% of the scheduled dose of IL-2. Hematologic toxicity was moderate and transient with no graft failure. Increases in eosinophil and lymphocyte counts were significant (P less than .05). Stimulation of the immune system was intense and prolonged, manifested by increase numbers of CD3+, CD3+DR+, CD3+ CD25+ lymphocytes, and natural killer (NK) cells (all P less than .01), and increase of Lymphokine-activated killers (LAK) and NK activities (P less than .01 and P less than .05). This study establishes the feasibility of a 6-day administration of rIL-2 after autologous BMT leading to a major immune activation 2.5 months after BMT.
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PMID:Hematologic and immunologic effects of the systemic administration of recombinant interleukin-2 after autologous bone marrow transplantation. 240 Aug 5

The human immunodeficiency virus type I (HIV-1) possesses powerful regulatory elements that control the rate of replication of HIV-1 and subsequent processing of HIV-1 genes. We have used this regulatory mechanism to drive expression of foreign genes inserted in retrovirus vectors. This approach was used to express the human IL-2 gene in IL-2-dependent mouse CTLL-2 cells to determine the role of autonomous growth in maintaining proliferation of virus-infected T lymphocytes during HTLV-1-induced adult T-cell leukemia (ATL). Expression of IL-2 sequences in IL-2-dependent mouse CTLL-2 cells resulted in autonomous growth of IL-2-independent CTLL-2 clones. Endogenous expression of IL-2 appeared to interrupt normal constraints of growth in that these IL-2-independent clones showed reduced cell-density-dependent inhibition but not a tumorigenic phenotype. IL-2-independent CTLL-2 clones did not secrete detectable quantities of IL-2 into culture supernatant and exhibited reduced sensitivity to the inhibitory effects of both IL-2 and IL-2 receptor antibody. These results suggest that the IL-2 autocrine loop within these cells involves intracellular IL-2/IL-2 receptor binding. The apparent lack of IL-2 production and poor responsiveness to IL-2 or IL-2 antibodies displayed by cell lines from ATL patients may be explained by an intracellular IL-2/IL-2 receptor autocrine loop.
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PMID:Autonomous growth of lymphoid cells following IL-2 expression from retrovirus vectors containing HIV-1 trans-acting elements. 240 56


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