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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new method for studying the physicochemical determinants of IgE-mediated activation of basophils is described. Rat basophil leukemia cells having IgE receptors were preincubated with monoclonal anti-dinitrophenyl IgE. These cells were then exposed to liposomes containing dinitrophenyl conjugated to phosphatidylethanolamine. The release of serotonin was measured. Using this system it was observed that liposomes containing dinitrophenyl conjugated to phosphatidylethanolamine by aminoethylformamidomethoxy acetyl (but not by caproic acid) were able to trigger the release of serotonin. "Solid" liposomes composed of dipalmitoylphosphatidylcholine and 2 mol % hapten were more potent inducers of serotonin release than "fluid" liposomes composed of dimyristoylphosphatidylcholine and hapten, but the fluid liposomes definitely triggered the cells to release serotonin. The addition of cholesterol to both types of liposomes enhanced their potency as activators and diminished the difference between the two types of phospholipid. This occurred despite the fact that cholesterol renders the solid liposomes fluid. Since it is unlikely that these fluid membranes can provide lateral forces that produce IgE-Fc receptor molecular clustering, we conclude that either receptor clustering is not necessary for basophil triggering, or molecular clustering is driven by molecular forces derived from IgE and components of the basophil cell.
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PMID:Mobile haptens in liposomes stimulate serotonin release by rat basophil leukemia cells in the presence of specific immunoglobulin E. 728 91

Spleen cells from 8-week-old, nonimmunized donor chickens can transfer resistance to a supralethal dose of the JMV leukemia line of Marek's disease (MD) to newly hatched, highly susceptible, histocompatible recipients. The population of cells transferring resistance has previously been shown to be non-T, non-B, and nonmacrophage in nature. We present data here showing that heavily x-irradiated spleen cells were unable to protect recipients from leukemia challenge. Both complement receptor-bearing and -lacking cells could confer resistance to newly hatched recipients. Fc receptor-bearing cells conferred significant protection to recipients, whereas spleen cells depleted of Fc receptor-bearing cells were unable to protect chickens from death after JMV challenge. This indicates that the population of spleen cells, which is moderately radiosensitive and which possesses Fc receptors, is responsible for the transfer of natural resistance to the malignancy in vivo.
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PMID:Transfer of natural resistance to Marek's disease (JMV) with nonimmune spleen cells. II. Further characterization of protecting cell population. 739 77

Stimulation of the CD40 antigen on normal B cells by crosslinking of anti-CD40 mAbs via their Fc receptor using a Fc gamma RII(CD32)-transfected mouse fibroblast cell line ('CD40 system') results in activation and proliferation. Not only normal B cells, but also malignant B cells fitting in the low-grade malignancy category such as chronic lymphocytic leukemia (CLL), hairy cell leukemia and follicular lymphoma could be induced to proliferation upon CD40 stimulation. Here, the 'CD40 system' has also been used to culture intermediate and high grade malignancies. Proliferation was measured by 3H-thymidine incorporation and cell counting after culture. Time curves showed that at day 7 most cultures were optimal. By flow cytometry, morphology and assessment of light chain restriction the monoclonal nature of the cultured B cells was proven. We confirmed that B cell malignancies with a more slowly evolving course, such as CLL (n=11), PLL (n=5), and low-grade NHL (immunocytoma and follicular cb/cc n=9), could successfully be cultured in the 'CD40 system'. In contrast, four out of seven cases of mantle cell lymphoma did not proliferate. Cases of precursor B lineage ALL (n=7), high grade NHL (n=3) and multiple myeloma (n=10) showed a heterogenous growth pattern. We conclude that the 'CD40 system', although not always successful, is a useful tool to culture a whole variety of B cell malignancies.
Leukemia 1996 Mar
PMID:Proliferation of B cell malignancies in all stages of differentiation upon stimulation in the 'CD40 system'. 864 67

We define by molecular, pharmacologic, and physiologic approaches the proximal mechanism by which the immunoglobulin superfamily member gp49B1 inhibits mast cell activation mediated by the high affinity Fc receptor for IgE (FcepsilonRI). In rat basophilic leukemia-2H3 cells expressing transfected mouse gp49B1, mutation of tyrosine to phenylalanine in either of the two immunoreceptor tyrosine-based inhibitory motifs of the gp49B1 cytoplasmic domain partially suppressed gp49B1-mediated inhibition of exocytosis, whereas mutation of both abolished inhibitory capacity. Sodium pervanadate elicited tyrosine phosphorylation of native gp49B1 and association of the tyrosine phosphatases src homology 2 domain-containing phosphatase-1 (SHP-1) and SHP-2 in mouse bone marrow-derived mast cells (mBMMCs). SHP-1 associated transiently with gp49B1 within 1 min after coligation of gp49B1 with cross-linked FcepsilonRI in mBMMCs. SHP-1-deficient mBMMCs exhibited a partial loss of gp49B1-mediated inhibition of FcepsilonRI-induced exocytosis at concentrations of IgE providing optimal exocytosis, revealing a central, but not exclusive, SHP-1 requirement in the counter-regulatory pathway. Coligation of gp49B1 with cross-linked FcepsilonRI on mBMMCs inhibited early release of calcium from intracellular stores and subsequent influx of extracellular calcium, consistent with SHP-1 participation. Because exocytosis is complete within 2 min in mBMMCs, our studies establish a role for SHP-1 in the initial counter-regulatory cellular responses whereby gp49B1 immunoreceptor tyrosine-based inhibition motifs rapidly transmit inhibition of FcepsilonRI-mediated exocytosis.
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PMID:gp49B1 inhibits IgE-initiated mast cell activation through both immunoreceptor tyrosine-based inhibitory motifs, recruitment of src homology 2 domain-containing phosphatase-1, and suppression of early and late calcium mobilization. 1002 1

Recently, highly efficient natural killer-like T immunologic effector cells called cytokine-induced killer (CIK) cells have been described. Most interestingly, CIK cells have been shown to eradicate established human lymphoma cells in a severe combined immunodeficient (SCID) mouse xenograft model in vivo. The current study was aimed at increasing the sensitivity of leukemia and lymphoma cells to CIK cells. In particular, the authors wanted to target CIK cells to leukemia and lymphoma cells via reverse antibody-dependent cellular cytotoxicity. Binding of an anti-CD3 monoclonal antibody to CIK cell cultures derived from patients with lymphoma was shown using flow cytometric analysis. For the target side, several B-cell lines were found to express CD19 on the cell surface. There was an impressive increase in sensitivity to CIK-mediated lysis of various lymphoma and leukemia cell lines by preincubation of the targets with a monoclonal antibody against CD3. This increase could be partially blocked by preincubation with anti-CD16 (Fc receptor III) and anti-CD32 (Fc receptor II) antibodies. These data suggest that the increase in cytotoxic activity is caused by Fc receptor-mediated antibody binding. Cytotoxic activity could be further increased by adding an anti-CD28 antibody in addition to anti-CD3. Finally, there was a further increase in sensitivity to CIK-mediated lysis of CD19+ malignant cells using the bispecific OKT3xHD37 antibody with specificity against CD3 and CD19. Interestingly, preincubation of malignant cells with an anti-CD3 monoclonal antibody followed by addition of the bispecific OKT3xHD37 antibody led to a further increase of cytotoxic sensitivity compared with the addition of the bispecific antibody alone. In conclusion, these data suggest that cytotoxic activity of immunologic effector cells can be increased not only by using the bispecific antibody OKT3xHD37 in vitro but also by preincubation of CD19+ leukemia and lymphoma cells with a monoclonal antibody against CD3. In addition, the immunostimulatory effect of the bispecific antibody OKT3xHD37 can be further increased by adding a monoclonal antibody against CD3.
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PMID:Targeting of natural killer-like T immunologic effector cells against leukemia and lymphoma cells by reverse antibody-dependent cellular cytotoxicity. 1083 59

Murine gp49, a 49-kDa type I transmembrane glycoprotein, is a member of the Ig-like receptors expressed on the surface of cells involved in natural immunity such as mast cells, NK cells, and macrophages. The two major subtypes, gp49A and gp49B, are encoded by two different genes adjacent to each other. gp49B contains an immunoreceptor tyrosine-based inhibitory motif in its cytoplasmic region and is known to function as an inhibitory molecule. In contrast, gp49A does not harbor any specific motif for signal transduction, nor has its physiological role been determined. Here we report on the stimulatory nature of gp49A by analyzing biochemical characteristics of chimeric molecules consisting of an ectodomain of Fc receptor and a C-terminal half of gp49A, namely the pretransmembrane, transmembrane, and cytoplasmic portions, expressed on the rat basophilic leukemia mast cell line. Cross-linking of the chimeric receptors evoked cytoplasmic calcium mobilization, PGD(2) release, and transcription of IL-3 and IL-4 genes, but did not elicit degranulation of the cells. The chimeric molecule could be expressed as a singlet and a homodimeric form on the cell surface. A pretransmembrane cysteine residue of gp49A was necessary for dimer formation. Dimerization was be necessary for their incorporation into glycolipid-enriched membrane fraction (GEM) upon cross-linking stimuli. The calcium mobilization response was inhibited by treatment of cells with methyl-beta-cyclodextrin, an inhibitor of GEM formation. Together with these results, it was strongly suggested that gp49A could be expressed as a homodimer and elicit activation signals that lead to calcium mobilization, eicosanoid production, and cytokine gene transcription through its incorporation into GEM.
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PMID:Stimulatory function of gp49A, a murine Ig-like receptor, in rat basophilic leukemia cells. 1104 24

We examined Fc receptor expression and function in normal and leukemic human immature B cells. Fc receptor expression increased with normal B cell maturation: CD32(+) cells composed 8.1% +/- 1.2% (mean +/- s.d.) of the least mature (CD34(+)CD10(+)), 19.2% +/- 5.7% of intermediate (CD34(-)CD10(+)), and 82.4% +/- 5.0% of mature (CD34(-)CD10(-)) bone marrow CD19(+) B cells. Forty-five of 57 primary B-lineage acute lymphoblastic leukemia samples and all six cell lines studied expressed Fc receptors. By RT-PCR and antibody staining, FcgammaRIIA was the Fc receptor predominantly expressed in these cells. FcgammaRIIA ligation in RS4;11 and 380 cells induced tyrosine phosphorylation of CD32, CD19, CBL, SYK, P13-K p85 and SHIP, as well as RasGAP association with tyrosine-phosphorylated p62(dok). These signalling events resulted in a marked suppression of leukemia cell growth. After a 7-day exposure to anti-CD32, the recovery of ALL cells cocultured with stroma was reduced to 5.5% +/- 2.8% of control values in 380 cells (n = 14), 19.4% +/- 6.1% (n = 8) in RS4;11, and 4.0% +/- 1.3% (n = 6) in KOPN55bi. CD32 ligation also reduced cell recovery in five of seven CD32(+) primary leukemia samples. Thus, FcgammaRIIA mediates signals that suppress the growth of lymphoid leukemia cells.
Leukemia 2002 Jul
PMID:Signals mediated by FcgammaRIIA suppress the growth of B-lineage acute lymphoblastic leukemia cells. 1209 51

Adult T-cell leukemia (ATL) develops in a small proportion of human T-cell leukemia virus I-infected individuals. Presently, there is no effective therapy for ATL. A murine model of ATL was produced by introducing leukemic cells (MET-1) from an ATL patient into nonobese diabetic/severe combined immunodeficient mice. The MET-1 cells are activated T cells that express CD2, CD3, CD4, CD25, CD122, and CD52. We evaluated the efficacy of Campath-1H (alemtuzumab; a humanized monoclonal antibody directed to CD52), alone and in combination with humanized anti-Tac (HAT) directed to CD25 (interleukin 2 receptor alpha) or with MEDI-507 directed to CD2. We observed that four weekly treatments with 4 mg/kg HAT significantly prolonged survival of MET-1-bearing mice. However, the survival of mice receiving 4 weeks of 4 mg/kg Campath-1H was significantly longer than that of the group receiving four weekly treatments with HAT (P < 0.001). Treatment with Campath-1H for 4 weeks led to a striking prolongation of the survival of MET-1 ATL-bearing mice that was comparable with that of tumor-free nontreated controls. Using Fc receptor (FcR) gamma(-/-) mice, we found that FcRgammas on polymorphonuclear leukocytes and monocytes are required for Campath-1H-mediated tumor killing in vivo. These results demonstrate that Campath-1H has therapeutic efficacy on ATL in vivo in that the life span of the Campath-1H treatment group was comparable with that of mice that did not receive a tumor or therapy. The main tumor killing mechanism with Campath-1H in vivo involves FcRgamma-containing receptors (e.g., FcRgammaIII) on polymorphonuclear leukocytes and macrophages that mediate antibody-dependent cellular cytotoxicity and/or trigger cross-linking induced apoptosis. This study provides support for a clinical trial of Campath-1H in the treatment of patients with T-cell leukemias and lymphomas.
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PMID:Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD52 monoclonal antibody, Campath-1H. 1455 36

We previously showed therapeutic efficacy of humanized anti-Tac (HAT), murine anti-Tac (MAT), and 7G7/B6 monoclonal antibodies, which recognize CD25, for human adult T-cell leukemia (ATL) in a murine model. In this study, we investigated the mechanism underlying the tumor-killing action mediated by these antibodies on an ATL model in nonobese diabetic/severe combined immunodeficient (SCID/NOD) wild-type mice that lack effective T and natural killer (NK) cells and in SCID/NOD Fc receptor common gamma chain knockout (FcRgamma-/-) mice. The ATL model was established by i.p. injection of human ATL cells (MET-1) into SCID/NOD wild-type or SCID/NOD FcRgamma-/- mice. HAT, MAT, and 7G7/B6 were given to the leukemia-bearing mice at a dose of 100 microg weekly for 4 weeks. The three antibodies inhibited the leukemia growth significantly in SCID/NOD wild-type mice, as monitored by serum levels of human beta2-microglobulin (P < 0.01), and prolonged survival of the leukemia-bearing SCID/NOD wild-type mice (P < 0.01) as compared with the control group. However, none of the antibodies manifested efficacy on the leukemia growth and survival of the SCID/NOD FcRgamma-/- mice bearing MET-1 leukemia. In a pharmacokinetics study, the blood concentrations of the radiolabeled antibodies decreased with time similarly in SCID/NOD wild-type and SCID/NOD FcRgamma-/- mice. Although NK cells may play a role in humans, in this murine model FcRgamma receptors on non-NK cells, such as polymorphonuclear leukocytes or monocytes, are required for the tumor-killing action of the antibodies directed toward CD25.
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PMID:Activating Fc receptors are required for antitumor efficacy of the antibodies directed toward CD25 in a murine model of adult t-cell leukemia. 1531 26

B-cell chronic lymphocytic leukaemia (B-CLL) is a heterogenous disease with a highly variable clinical course and analysis of zeta-associated protein 70 (ZAP-70) and CD38 expression on B-CLL cells allowed for identification of patients with good (ZAP-70-CD38-) and poor (ZAP-70+CD38+) prognosis. DNA microarray technology was employed to compare eight ZAP-70+CD38+ with eight ZAP-70-CD38- B-CLL cases. The expression of 358 genes differed significantly between the two subgroups, including genes involved in B-cell receptor signaling, angiogenesis and lymphomagenesis. Three of these genes, that is, immune receptor translocation-associated protein 4 (IRTA4)/Fc receptor homologue 2 (FcRH2), angiopoietin 2 (ANGPT2) and Pim2 were selected for further validating studies in a cohort of 94 B-CLL patients. IRTA4/FcRH2 expression as detected by flow cytometry was significantly lower in the poor prognosis subgroup as compared to ZAP-70-CD38- B-CLL cells. In healthy individuals, IRTA4/FcRH2 protein expression was associated with a CD19+CD27+ memory cell phenotype. ANGPT2 plasma concentrations were twofold higher in the poor prognosis subgroup (P<0.05). Pim2 was significantly overexpressed in poor prognosis cases and Binet stage C. Disease progression may be related to proangiogenic processes and strong Pim2 expression.
Leukemia 2006 Oct
PMID:Gene expression signatures separate B-cell chronic lymphocytic leukaemia prognostic subgroups defined by ZAP-70 and CD38 expression status. 1693 41


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