Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe monoclonal antibodies (mAbs: anti-MaG-1, TGI-1, TGI-5, and TGI-6) that block the proliferation of AML-193 cells in response to GM-CSF or IL-3 and do not affect the proliferation of AML-193 cells in response to G-CSF and IL-2-driven proliferation of Kit 225 cells. However, none of the mAbs tested had any stimulative effect on the proliferation of AML-193 cells. The mAbs (anti-MaG-1, TGI-1, -5, and -6) could inhibit the binding of [125I]GM-CSF to AML-193 cells. We were able to purify MaG-1 Ag by anti-MaG-1 affinity chromatography. Thus, the MaG-1 Ag and the Ags recognised by mAbs (TGI-1, -5, and -6) may be associated with the receptor for GM-CSF or IL-3 or a structure close to the receptor for GM-CSF or IL-3.
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PMID:Monoclonal antibodies that specifically inhibit GM-CSF- and IL-3-dependent growth of human monocytic leukemia cells. 256 Sep 32

The presence of CD25 and HC2 antigens in 66 different patients with acute myeloid leukemia (AML) was investigated. The expression of both antigens was observed in 32% of AML cells. Dual fluorescence staining experiments performed in 5 AML patient cells showed that CD25 and HC2 antigens were simultaneously expressed in a single cell. The expression of both antigens was mainly observed in the M4 and M5 subtypes of AML. Although immunopurified IL-2 was able to block the binding of anti-CD25 monoclonal antibody to the AML cells, the IL-2 receptor did not appear to be functional.
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PMID:Differential expression of CD25 and HC2 antigens on subtypes of acute myeloid leukemias. 265 80

We describe a case of acute nonlymphocytic leukemia (ANLL) in a patient with a constitutional chromosome anomaly, inv(4)(p16q26). The patient had extensive occupational exposure to toxic chemicals. Reports of constitutional or acquired chromosome inversions in human malignancies are quite uncommon. The constitutional changes associated with hematologic malignancies include trisomy 21, balanced translocations, deletions, and sex chromosome anomalies. The breakpoints on chromosome 4 in our case are 4p16, to which the murine leukemia viral (v-raf) oncogene, pseudogene 1, has been mapped, and 4q26, which is the locus of the IL-2 gene. Activation of these genes could have played a role in the pathogenesis of the patient's leukemia.
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PMID:Acute nonlymphocytic leukemia in a patient with a constitutional inv(4). 273 Nov 38

Recent studies have shown that IL-2R are composed of at least two polypeptide chains of 55 kDa (Tac or alpha-chain) and 70 to 75 kDa (p70 or beta-chain). The association of both chains forms high affinity IL-2R, whereas each chain alone binds IL-2 with a low (alpha-chain) or intermediate (beta-chain) affinity. So far, the p70 peptide has been found, in the absence of the Tac peptide, on the surface of lymphoid cells of T, B, or NK lineage. In this study, we investigated whether leukemic cells of various hemopoietic lineages expressed the p70 IL-2-binding protein. We found that both fresh leukemic cells obtained from patients, and cells from established leukemic lines of T cells, B cell, and myeloid origin constitutively expressed a p70 IL-2-binding protein on their surface, as detected by affinity cross-linking of radioiodinated IL-2. IL-2 binding and cross-linking to these cells was completely inhibited in the presence of an excess unlabeled rIL-2, but not with an anti-Tac mAb. Binding experiments on pre-B and myeloid cell lines revealed intermediate affinity IL-2R, whereas both high and intermediate affinity IL-2R were detected in T leukemic cells. The intermediate affinity binding of 125I-rIL-2 to the leukemic cell lines MOLT4 and Reh6 was inhibited by the TU27 mAb, which recognized the p75 chain of IL-2R. Moreover, the TU27 mAb could stain the K562, KM3, and MOLT4 (weakly) cell lines by indirect immunofluorescence. A high dose of rIL-2 (400 U/ml) enhanced the proliferation of cells from one out of three patients with acute myeloblastic leukemia, but it did not induce differentiation of the cells in any of three cases. Thus the finding of p70 IL-2-binding molecules on immature lymphoid and nonlymphoid hemopoietic cells should disclose new biologic functions for IL-2.
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PMID:Presence of a p70 IL-2-binding peptide on leukemic cells from various hemopoietic lineages. 278 58

Activation and expansion in culture with rIL-2 of peripheral blood (PB) and/or bone marrow (BM) specimens derived from children with ALL and ANLL, with active disease (AP) and in remission were studied (RP). Baseline NK cytolytic activity from AP was found to be depressed, whereas RP-derived cells had normal NK activity, as assayed against K562 targets. Culture in rIL-2 significantly enhanced the NK activity of both AP- and RP-derived cells and generated LAK activity, as assayed by 4-hour 51Cr release, against NK-resistant Raji cell line and against fresh, allogeneic, and autologous tumor cells. Lytic activity against fresh, cryopreserved leukemia blasts was of lower than that found against cell lines. In three patients higher lytic activity against autologous than against allogeneic blasts was demonstrated. Expansion in culture with rIL-2 varied from twofold to 120-fold. rIL-2 activation and expansion was better in RP than in AP. The predominant phenotype of activated cells, as determined by flow cytometry, was [mean % (SD)]: CD3- = 54 (12), CD8+ = 55 (17), and NKH1+ = 26 (7). The consistently high level of CD8+ cells was accompanied by very low levels of CD4+ cells: mean = 11% (14). Double-marker analysis showed mean of 33% (10) for CD3+/NKH1+ cells and mean = 32 (11) for CD8+/NKH1+ cells, implying that these populations were overlapping. Kinetics of expression of cell surface markers during 2 to 3 weeks in culture showed that CD8+ and NKH1+ enrichment occurred during the first week and lasted for up to 4 weeks, whereas CD4+ expression decreased after the second week. A significant decrease in the expression of IL-2 receptors (CD25) was observed from the second week of culture. This study shows the feasibility of in vitro generation of killer cells from PB and BM of pediatric leukemia patients.
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PMID:Interleukin-2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients: II. Feasibility of LAK generation in children with active disease and in remission. 279 Jan 93

A proportion of blasts from five of 10 cases of AML expressed receptors for IL-2 (IL-2R) when tested directly ex-vivo with monoclonal antibodies against the receptor. After in-vitro stimulation with various agents including TPA, gamma interferon and colony stimulating factor, the purified blast cells of all cases of AML tested (10 of 10) showed high levels (50-90% cells positive) of IL-2R expression. Granulocytic cells from the promyelocyte stage onwards lacked IL-2R both before and after in-vitro stimulation. In contrast, leukaemic promonocytes and normal peripheral monocytes expressed IL-2R both before and after stimulation. The receptors were detected with two different monoclonal antibodies (anti-Tac and 4H3--both IgG 2a antibodies) by indirect rosetting. In selected experiments, results were confirmed by fluorescence microscopy and by the APAAP technique. Normal monocytes possessed only small amounts of IL-2R since positivity was clearly detectable only by the indirect rosette assay. Irrelevant IgG 2a first-layer and second-layer-only controls were always negative. The endogenous nature of the IL-2 receptors was demonstrated by re-expression after capping and shedding. That the antigens detected were true IL-2R was confirmed by the fact that monoclonal antibody staining was blocked by recombinant IL-2. The restricted expression of IL-2R on early granulocytic and on monocytoid cells raises the possibility that IL-2 is important in the proliferation of these cell types.
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PMID:Certain myeloid cells possess receptors for interleukin-2. 302 33

We have studied the interaction of 35S-labeled recombinant IL-3 with the acute myelogenous leukemia cell line, KG-1. 35S-IL-3 bound to these cells in a time dependent, saturable, and specific manner at 4 degrees C. Scatchard transformation of binding isotherms demonstrated the existence of a small number (200) of binding sites, with an apparent dissociation constant of 70-105 pM. After a temperature shift from 4 degrees C to 37 degrees C, surface-bound 35S-IL-3 was rapidly internalized and processed into a trichloroacetic acid soluble form that was released into the medium. Experiments to address the specificity of the IL-3 binding site revealed that neither human IL-2, M-CSF, erythropoietin, transferrin, bovine insulin, nor murine nerve growth factor compete with IL-3 for binding to KG-1 cells. Both human and gibbon recombinant IL-3 and, surprisingly, human recombinant GM-CSF effectively competed the binding of the labeled IL-3 to these cells at 4 degrees C. The competition by GM-CSF was found to be concentration dependent, but much higher concentrations were required to achieve the levels obtained with IL-3. These results suggest that GM-CSF may also interact with the high-affinity IL-3 binding site on KG-1 cells or, alternatively, that GM-CSF binding to its own receptor may decrease the affinity of the IL-3 receptor for its ligand.
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PMID:Specific binding, internalization, and degradation of human recombinant interleukin-3 by cells of the acute myelogenous, leukemia line, KG-1. 304 27

We have demonstrated that unstimulated highly-enriched NK cells have the capability to inhibit the growth of fresh clonogenic leukemic cells from AML, CML and preleukemic patients. The NK-cell population mediating antileukemic reactivity exhibited LGL morphology and NKH1 and CD16 phenotype. The inhibition of leukemic growth could be mediated by cell-to-cell contact or by soluble factor produced by NK cells. Antileukemia activity was only detectable when enriched population of LGL was utilized; NW-filtered lymphocyte population did not exhibit leukemia-inhibitory effect. However, such activity could be generated after culture of the latter effector cells with IL-2. The leukemia directed IL-2 activated effector cells were characterized as NK cells. The data reported here provide new insight into host factors which may control leukemia growth and indicate the possible future application of NK cells for therapy of leukemia.
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PMID:Inhibition of clonogenic growth of fresh leukemia cells by unstimulated and IL-2 stimulated NK cells of normal donors. 350 Oct 42

In this study we have demonstrated that natural killer (NK) cells adhere to elements of the bone marrow stroma (BMS) including fibroblasts, fibronectin and laminin but not to collagen type I, vitronectin and hyaluronic acid. NK cells bind to fibronectin and laminin using the beta 1 integrins VLA-4 and VLA-5, and VLA-6 respectively. The mechanism of adhesion to bone marrow fibroblasts is more complicated with beta 1 and beta 2 integrins being partially responsible but the majority of adhesion remaining unexplained. IL-2 stimulation of NK cells resulted in an increase in the expression of adhesion molecules involved in binding of NK cells to bone marrow fibroblasts (BMF) and extracellular matrix (ECM) proteins including the beta 1 chain CD29, alpha chains of VLA-4 and 5, beta 2 chain CD18 and alpha L chain CD11a. A marked increase in expression of beta 7 was also observed. There was a significant increase in the adhesion of NK cells to fibronectin in response to IL-2 treatment. NK cells also bound more strongly to BMF following IL-2 treatment although the development of cytotoxicity appeared to interfere with the adhesion assay. NK cells competitively inhibit the binding of AML blasts but not ALL blasts to BMF. Mechanisms underlying the inhibition of leukemic growth by NK and LAK cells may include direct and cytokine mediated cytotoxicity and perturbation of the interaction of leukemic blasts with the bone marrow stroma which is essential for blast cell survival.
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PMID:Natural killer cells adhere to bone marrow fibroblasts and inhibit adhesion of acute myeloid leukemia cells. 759 92

It has been suggested that cord blood T cells may be less able to mediate GVHD than marrow-derived T cells due to their naive status. A decreased potential for GVHD may be advantageous for allogeneic transplant, but this benefit might be counteracted by loss of the GVHD associated graft-versus-leukemia (GVL) effect. The GVL potential of cord blood could be doubly compromised since cord blood NK cell activity is also decreased. To assess these issues we have performed extensive comparative functional and immunophenotypic evaluations of cord and adult mononuclear cells. We found a somewhat reduced alloproliferative, allostimulatory and allocytolytic capacity of cord blood mononuclear cells in bulk assays but not by limiting dilution assays. Immunophenotyping revealed no significant differences in the proportion of major lymphocyte subsets with the exception of the previously recognized predominance of CD45RA+ cells in both CD4 and CD8 cord blood T cells. Cord blood T cells expressed normal percentages of the cellular adhesion molecules, CD11a, CD18 and LFA-3; however, the antigen density of each of these molecules was less than that found on adult T cells. Fewer resting cord blood T cells expressed CD54, the ligand for LFA-1. Cord blood B cells and monocytes expressed normal levels of HLA-class I and HLA class II DR, DP and DQ antigens, suggesting that the decreased expression of cellular adhesion molecules or their receptors rather than a decrease in expression of HLA might have contributed to the lower alloreactivity of cord blood. Although the percentages of NK cells and NK cell subsets in adult and cord blood were similar our data confirmed that cord blood has very low NK lytic activity. In contrast, LAK activity was much more readily induced in cord blood compared with adult PBMC, a finding which could be explained in part by a higher frequency of LAK precursors and a more rapid expansion of NK cells in response to culture with medium containing of NK cells in response to culture with medium containing IL-2. Cord blood LAK cells were readily able to lyse fresh leukemia targets from patients with ALL, AML and CML. The data indicate that although the alloreactive potential of cord blood cells may be somewhat decreased, it is not absent and must be considered a factor in cord blood transplants. LAKp with the potential to lyse leukemia are present in increased numbers in cord blood and might contribute to the GVL effect of a cord blood transplant.
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PMID:Characterization of the alloreactivity and anti-leukemia reactivity of cord blood mononuclear cells. 759 66


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