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)

NK cells and certain CTL can recognize and lyse targets without restriction by the MHC. NK cells do not express CD3/TCR complexes and the membrane receptors participating in MHC-unrestricted cytotoxicity are largely unknown. We demonstrate that YT2C2, a human NK leukemia cell line, expresses the CD28 differentiation Ag and can spontaneously lyse both murine and human cell lines expressing B7, a B cell- activation Ag that is a ligand for CD28. The participation of CD28/B7 interactions in MHC-unrestricted cytotoxicity mediated by YT2C2 cells was demonstrated by correlation of target sensitivity with levels of B7 expression, inhibition of cytotoxicity by anti-CD28 or anti-B7 mAb, and by making both murine and human cell lines susceptible to YT2C2-mediated lysis by genetic transfection with expression vectors containing B7 cDNA. However, CD28/B7 interactions alone were insufficient to initiate cytotoxicity. mAb inhibition experiments and selection of CD54- (intercellular adhesion molecule-1) deficient B cell targets indicated that CD11a/18 (lymphocyte function-associated Ag-1) also cooperated in CD28/B7-dependent cytotoxicity. The requirement for both CD28/B7 and lymphocyte function-associated Ag-1/intercellular adhesion molecule-1 interactions in YT2C2-mediated MHC-unrestricted cytotoxicity was confirmed by demonstrating that efficient lysis of murine L cells required cotransfection with both B7 and intercellular adhesion molecule-1. These findings support the concept that MHC-unrestricted cytotoxicity may not be due to a unique receptor, but may result from interactions between an appropriate array of "adhesion" molecules with their ligands.
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PMID:Involvement of CD28 in MHC-unrestricted cytotoxicity mediated by a human natural killer leukemia cell line. 138 31

Murine mast cells produce cytokines in response to cross-linking of high affinity receptors for IgE (Fc epsilon RI). Murine mast cells also express the two types of low-affinity receptors for IgG, murine (m)Fc gamma RII, and mFc gamma RIII. We examined the ability of mFc gamma R to trigger a cytokine response such as TNF-alpha production by mast cells. We found that the mFc gamma RII- and mFc gamma RIII-positive mouse mastocytoma cells MMC-1 released TNF-alpha when challenged with F(ab')2 fragments of the rat anti-mFc gamma RII/III 2.4G2 mAb and mouse anti-rat IgG F(ab')2. The release of TNF-alpha was preceded by an increase in TNF-alpha transcripts. mFc gamma RII and mFc gamma RIII have 95% homologous extracellular domains but unrelated transmembrane and intracytoplasmic (IC) domains. mFc gamma RII are single chain receptors whereas mFc gamma RIII associate with a homodimeric gamma-chain that also associates with Fc epsilon RI and TCR. In order to analyze the ability of mFc gamma RII and III to trigger the synthesis of TNF-alpha, we studied RBL-2H3 cells transfected with corresponding cDNA. Rat basophilic leukemia (RBL) transfectants expressing mFc gamma RIII produced TNF-alpha in response to 2.4G2 F(ab')2, but not transfectants expressing mFc gamma RII. Non-transfected RBL cells and mFc gamma RII- or mFc gamma RIII-expressing transfectants, however, released TNF-alpha in response to a rat IgG2a mAb. The respective roles of the alpha and gamma subunits of mFc gamma RIII were examined by studying the production of TNF-alpha by RBL cells expressing deletant and chimeric mFc gamma R. The deletion of intracellular amino acids of the Fc gamma RIII alpha subunit did not prevent 2.4G2 F(ab')2 from triggering the synthesis of TNF-alpha. The substitution of the IC domain of mFc gamma RII for that of mFc gamma RIII gamma, but not that of Fc gamma RIII alpha, enabled 2.4G2 F(ab')2 to trigger the release of TNF-alpha by RBL transfectants. A cytokine response can therefore be induced in mouse and rat mast cells through Fc gamma R. This response is triggered upon cross-linking of mFc gamma RIII but not mFc gamma RII. It depends on the IC sequences of the gamma but not of the alpha subunit of mFc gamma RIII.
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PMID:Induction of tumor necrosis factor-alpha production by mast cells via Fc gamma R. Role of the Fc gamma RIII gamma subunit. 138 72

The effect of SK&F 96365 (1-(beta-[3-(4-methoxyphenyl)propoxyl]-4- methoxyphenethyl)-1H-imidazole hydrochloride), a recently synthesized inhibitor of receptor-mediated calcium entry, was investigated on human hematopoietic cell lines. We found that treatment of the T-cell leukemia line Jurkat with SK&F 96365 inhibited the Ca2+ influx triggered by antibodies against the CD3/TCR complex, while the inositol trisphosphate-dependent Ca2+ release from intracellular stores remained intact. A 50% inhibition of the Ca2+ influx was obtained with 5 microM SK&F 96365, while higher concentrations of the drug blocked the CD3-dependent Ca2+ influx completely. In addition to its blocking of the Ca2+ influx, treatment with SK&F 96365 was found to accumulate mitotic cells. The drug (5 microM) imposed a total cell cycle arrest in G2/M. The mitosis block could be reversed by removal of the inhibitor from the cultures, while elevation of intracellular or extracellular Ca2+ did not restore cell cycle progression. This suggests that the cell cycle block induced by SK&F 96365 is not directly related to its action as an inhibitor of receptor-mediated calcium entry. Our findings indicate that SK&F 96365, in addition to its ability to inhibit receptor-triggered Ca2+ influx, offers a new method for imposing a reversible mitosis arrest in hematopoietic cell lines.
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PMID:Mitosis-arresting effect of the calcium channel inhibitor SK&F 96365 on human leukemia cells. 139

The paper describes a case of Philadelphia (Ph) positive acute lymphoblastic leukaemia (ALL) presenting with high white cell count and central nervous system involvement. Immunophenotypically the case was characterized as common ALL. The t(9;22) abnormality corresponded to a rearrangement within the breakpoint cluster region gene, while antigen receptor gene studies showed multiple rearrangements of the immunoglobulin heavy chain gene (IGH) concomitant with a single rearrangement of the T cell receptor beta chain gene (TCR beta). We speculate that this case represents the neoplastic transformation of a stem cell, the Ph abnormality being involved in the early steps of transformation. It is conceivable that the IGH but not the TCR beta gene was accessible to recombination within the malignant clone, thus generating the multiple rearrangements observed. If this is the case, these findings would appear to be compatible with the hypothesis that antigen receptor gene rearrangements may be partly dependent on the accessibility of the corresponding genetic loci.
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PMID:A complex pattern of antigen receptor gene rearrangements in a case of Philadelphia positive acute lymphoblastic leukaemia. 140 37

We investigated the surface markers, cell-function, clonality, and the association of IL-2 receptors and a second messenger of src family of tyrosine kinase p56lck in IL-2 signal transduction of the leukemic cells of 12 patients with large granular lymphocytic leukemia (LGL leukemia). The leukemic cells of 5 patients were CD3+ and 5 of them were CD3-. In three patients with CD3- leukemia examined, one showed karyotype abnormality of 46, XY, -10, +mar and the delta gene of TCR was rearranged in one patient. The TCR of the leukemic cells of a patient MH with CD3+, CD4 and CD8 (double positive marker: DP) recognised rabbit IgG presented by macrophages. The recognition was class II restricted. We examined the expression pattern of CD8 subunits and found that DP leukemic cells commonly expressed CD8 alpha+ beta-. These results suggested that DP leukemic cells were CD4+ T cells and expressed CD8 alpha secondarily. The p75 IL-2 receptors were detected, however, the modulation of p56lck in the process of IL-2 signal transduction were not found out. There was no association between p75 and p56lck when leukemic LGL cells proliferated on stimulation with IL-2.
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PMID:[Large granular lymphocytic leukemia]. 151 40

Specific chromosomal translocations are one of the cytogenetic characteristics of hematopoietic malignancies. The application of molecular biological techniques has led to important insight into the molecular consequences, accompanied by the chromosomal translocations. Specific oncogenes and related genes activated by the translocations have been identified at the translocation breakpoints. Translocated oncogenes are deregulated by their juxtaposition to enhancers of Ig or TCR genes, resulting in their overexpressions in some lymphoid tumors. Alternatively, they are activated by gene fusion, resulting in a chimeric oncoprotein, as seen in Ph1-positive leukemia. The molecular consequences by chromosomal translocation in hematopoietic malignancies is focused here.
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PMID:[Activation of oncogenes by chromosomal translocation in hematopoietic tumors]. 151 55

Members of the Ets family of proto-oncogenes encode sequence-specific transcription factors that bind to a purine-rich motif centered around a conserved GGA trinucleotide. Ets binding sites have been identified in the transcriptional regulatory regions of multiple T cell genes including the T cell receptor alpha and beta (TCR-alpha and -beta) enhancers and the IL-2 enhancer, as well as in the enhancers of several T cell-trophic viruses including Maloney sarcoma virus, human leukemia virus type 1, and human immunodeficiency virus-2. T cells express multiple members of the Ets gene family including Ets-1, Ets-2, GABP alpha, Elf-1, and Fli-1. The different patterns of expression and protein-protein interactions of these different Ets family members undoubtedly contribute to their ability to specifically regulate distinct sets of T cell genes. However, previous studies have suggested that different Ets family members might also display distinct DNA binding specificities. In this report, we have examined the DNA binding characteristics of two Ets family members, Ets-1 and Elf-1, that are highly expressed in T cells. The results demonstrate that the minimal DNA binding domain of these proteins consists of adjacent basic and putative alpha-helical regions that are conserved in all of the known Ets family members. Both regions are required for DNA binding activity. In vitro binding studies demonstrated that Ets-1 and Elf-1 display distinct DNA binding specificities, and, thereby interact preferentially with different naturally occurring Ets binding sites. A comparison of known Ets binding sites identified three nucleotides at the 3' end of these sequences that control the differential binding of the Ets-1 and Elf-1 proteins. These results are consistent with a model in which different Ets family members regulate the expression of different T cell genes by binding preferentially to purine-rich sequences that share a GGA core motif, but contain distinct flanking sequences.
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PMID:Evolutionarily conserved Ets family members display distinct DNA binding specificities. 156 4

A 59-year-old man was admitted because of generalized lymphadenopathy with fever and vomiting. His peripheral blood showed leukocytosis with a WBC of 93,500/microliters, and the bone marrow picture revealed a predominance of blast cells. The blasts were negative for peroxidase, alpha-naphthyl butyrate esterase and PAS, and had the phenotype of CD 7, 13 and 33 positive. A diagnosis of AML M0 was made, based on the criteria of the NCI-sponsored workshop in 1988. His initial status had been compromised by acute renal failure which necessitated hemodialysis. He responded partially to chemotherapy consisting of daunorubicin, cytarabine and prednisolone. However leukemia recurred and the patient suffered from various episodes of infection and died six months after admission. The Southern blotting showed the germ line configuration for TCR-beta chain and immunoglobulin heavy chain genes. No messenger RNA was detected for myeloperoxidase, c-myc and c-jun, while c-fms, c-fos and c-myb were expressed on Northern blotting. It is intriguing to detect c-fms and c-fos expression in these poorly differentiated leukemic cells.
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PMID:[A case report of AML M0:CD7, 33 (+) AML M0 case initially presented with cervical lymphadenopathy]. 160 10

Several murine lymphoid cell lines have been tested for specific capacity to localize in thymus. These are all continuous, cloned Radiation leukemia virus-induced cell lines which have a common phenotype resembling lymphoid stem cells or immature T cells. Since each of these cell lines has a cloning efficiency approaching 100%, the number of cells which enters thymus during a 3 h homing assay has been estimated by limit dilution cloning analysis taking into account extra-binomial variation caused by individual mice. Only two out of seven of these cell lines have been found to have this specific property. These two cell lines, 16C1 and 5C2B, have been characterized as immature lymphoid cells, bearing no rearrangement at the TCR gamma and beta loci, and having the phenotype of CD3+CD4-CD8-, immature T cells. A maximum number of 2000 16C1 cells and 2500 5C2B cells can enter thymus during a 3 h homing assay, suggesting a limited number of sites in thymus to which these cells can bind. The capacity of 16C1 to enter thymus in low frequency has been found to be a stable property and was not increased by repetitive passage through mouse thymus. Using this assay, we have also been able to confirm that entry of 16C1 cells into thymus can be inhibited by antibody specific for the Ly24 (Pgp-1) molecule.
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PMID:Characterization of lymphoid cell lines from murine spleen which can localize in thymus. 162 95

We have successfully isolated continuous T cell lines from murine spleen which have been induced to proliferate after in vitro exposure to the murine leukemia virus RadLV. Cell lines isolated from several strains of mice have an "immature" phenotype and are immortalized CD4- CD8- CD3+ cell lines. Cell lines of similar phenotype have now been derived from many individual mice, after spleens have been infected with two different RadLV viruses, a leukemogenic and a nonleukemogenic isolate. Among cell lines induced with RadLV/C6VL, an unusually high proportion of cells was found to bind the 124-40 anticlonotypic antibody specific for the alpha beta TCR expressed by C6VL/1 cells which produces RadLV/C6VL. This was not reflected in cell lines induced with the RadLV/V13 isolate nor in various lymphocyte subsets freshly isolated from normal mice, or induced to proliferate in culture. Cells expressing a common TCR structure would appear to be appropriate targets for in vitro proliferation and transformation induced by RadLV.
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PMID:Preferential expression of a common T cell receptor structure by T cells induced to proliferate in vitro with a murine retrovirus. 164 84


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