Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rat basophilic leukemia RBL-2H3 mast cell line is widely used for studies of the structure and function of the high affinity IgE receptor (Fc epsilonRI). Here we report on a simple method to isolate large numbers of intact RBL-2H3 cells from tumors produced by injection of the cells into newborn rats. Collagenase treatment of rat tumors yields approximately 3.5 x 10(8) viable cells/animal. Aggregating Fc epsilonRI on these cells induced tyrosine phosphorylation of proteins including the protein tyrosine kinase Syk. This procedure should prove useful for the isolation and characterization of cellular molecules important for mast cell and basophil function.
 ...
PMID:Large scale isolation of intact rat basophilic leukemia (RBL-2H3) cells. 903 5

Recently, the expression of the mRNA for the proto-oncogene c-fos following activation of the high-affinity receptor for immunoglobulin E in rodent mast cells has been reported. In the present study we investigated different biochemical events that may play a role in signal transduction pathways culminating in the expression of c-fos mRNA in rat basophilic leukaemia cells. Similar to IgE-mediated cell degranulation we demonstrated inhibition of the c-fos signal in the absence of calcium and after preincubation of cells with the protein tyrosine kinase inhibitor genistein. Activation of RBL-2H3 cells by short term PMA treatment failed to induce cell degranulation or expression of mRNA for c-fos. Depletion of protein kinase C by PMA pre-treatment resulted in substantial inhibition of the c-fos signal. In contrast to IgE-mediated cell degranulation, expression of mRNA for c-fos was not dependent on continued receptor aggregation. In addition, we demonstrate that c-fos mRNA expression is not restricted to Fc epsilon RI activation but can be induced by a variety of IgE independent mechanisms including calcium influx by ionophore A 23187 and stimulation of G proteins.
 ...
PMID:Expression of mRNA for the proto-oncogene c-fos in rat basophilic leukaemia cells. 906 32

We constructed a recombinant plasmid which expresses antisense src RNA after dexamethasone (Dexa) treatment, and transfected it into U937 human monoblastic leukemia cells (U937-ASRC). Induction of antisense src RNA expression diminished the amounts of c-Src and its protein tyrosine kinase (PTK) activity in U937-ASRC cells. The declines in c-Src and its PTK activity subsequently reduced the proliferation of U937-ASRC cells. To elucidate the growth signal transduction pathway downstream of c-Src, tyrosine phosphorylation of Shc was examined in U937-ASRC cells treated with Dexa. The decline in c-Src by induction of antisense src RNA expression decreased the level of tyrosine phosphorylation of Shc. Immunoprecipitated c-Src directly phosphorylated immunoprecipitated Shc on tyrosine residues in vitro. The amounts of Grb2 and Sos co-immunoprecipitated with Shc were decreased after Dexa treatment. However, the amount of Sos co-immunoprecipitated with Grb2 was apparently not affected by Dexa treatment. These results indicate that Grb2 and Sos constitutively associate with each other in U937 cells. Furthermore, the level of phosphorylation on tyrosine (204) essential for MAP kinase activation was decreased after Dexa treatment. Taken together with all these findings, it is suggested that c-Src directly phosphorylates Shc on tyrosine residues, which in turn binds to Grb2 constitutively associated with Sos to form a Shc-Grb2-Sos complex, and that the complex formation is coupled with MAP kinase activation mediated by Ras activation in U937 cells.
Leukemia 1997 Apr
PMID:Antisense src expression inhibits tyrosine phosphorylation of Shc and its association with Grb2 and Sos which leads to MAP kinase activation in U937 human leukemia cells. 909 89

c-Abl protein tyrosine kinase activity is tightly regulated in vertebrate cells. Several mutations can activate Abl and convert it into an oncogene. In man, chromosomal translocations result in fusion proteins associated with chronic myelogenous leukemias and some acute lymphocytic leukemias. In viral forms of abl, gag sequences are fused to Abl portions resulting in a deletion of N-terminal sequences. To study c-Abl activity in a cellular environment likely to lack specific regulators, we have expressed human c-Abl in Schizosaccharomyces pombe in an inducible fashion. c-Abl causes growth arrest followed by death of the cells. Mutations in the SH2 domain or in the autophosphorylation site dramatically reduce the ability of Abl to confer the growth arrest phenotype and to phosphorylate endogenous proteins, suggesting a fundamental role of these structures in the activity of the enzyme. An SH3 domain deletion mutant of Abl is as active as c-Abl in yeast indicating that there is no intrinsic regulation of c-Abl occurring via the SH3 domain and suggesting that the inhibitory effect of the SH3 domain observed in cells of vertebrate origin is mediated by a factor that is absent in fission yeast. We have used this assay to functionally screen a human cDNA library for molecules able to counteract the lethal effect of c-Abl expression. We are currently in the process of characterising the isolated clones. We hope to identify among them the molecule(s) responsible for regulating c-Abl activity in human cells.
Leukemia 1997 Apr
PMID:A functional screen for regulators of the c-Abl protein tyrosine kinase. 920 75

Some anaplastic large cell lymphomas (ALCLs) carry a specific chromosomal translocation, t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kDa protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning revealed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al.). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathological comparison between p80-positive and -negative ALCLs revealed that p80-positive cases occurred in a far younger patient age group and the patients showed a far better 5-year survival rate. These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically, and should be differentiated from p80-negative ALCL.
Leukemia 1997 Apr
PMID:Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity. 920 50

Bryostatin 1 (bryo1), a naturally occurring macrocyclic lactone derived from the marine bryozoan Bugula neritina is a potent protein kinase C (PKC) activator. In this report, we investigated the role of c-fyn protein, a src-related protein tyrosine kinase (PTK), during bryo1-induced monocytic differentiation in a human leukemia cell line, THP-1. Bryo1 treatment for 24 h inhibited the proliferation of THP-1 cells and caused a major fraction of them to become adherent cells with distinct monocyte/macrophage features and enhanced expression of M-CSF receptors (M-CSFR), a hallmark of mature macrophages. The THP-1 cells in control cultures expressed low but detectable levels of c-fyn proteins. Treatment of THP-1 cells with bryo1 resulted in an enhanced expression of c-fyn proteins, but not c-lyn proteins, another member of the src-family of kinases. The bryo1 treatment also enhanced the levels of both c-fyn tyrosine kinase and autophosphorylation activities in THP-1 cells. Using a combined immunoprecipitation and immunoblot analysis, bryo1 was shown to promote an enhanced association between c-fyn kinase and M-CSFR. The inducing activity of bryo1 was associated with PKC activation; treatment of THP-1 cells with bryo1 led to a rapid and transient elevation of total PKC activity in THP-1 cells. These results show that enhanced expression and activation of fyn kinases are critical events associated with monocytic differentiation induced by bryo1 in THP-1 cells. Our findings may be of clinical relevance, as bryo1 has been used in clinical trials of cancer patients.
 ...
PMID:Bryostatin 1 (bryo1)-induced monocytic differentiation in THP-1 human leukemia cells is associated with enhanced c-fyn tyrosine kinase and M-CSF receptors. 922 66

Abelson murine leukemia virus transforms pre-B cells in vitro and induces rapid-onset pre-B-cell lymphoma in vivo. Expression of an active v-Abl protein tyrosine kinase is required for the oncogenic functions of the virus. Despite the strong growth-stimulatory signal provided by v-Abl, the virus-induced tumors are clonal or oligoclonal, and changes in the growth and oncogenic potential of in vitro transformants occur during the derivation of the cell lines. Both of these features suggest that v-Abl expression must be complemented by changes in expression of one or more cellular genes for cells to acquire a fully malignant phenotype. Such genes could include other oncogenes or tumor suppressor genes. Among the latter is Tp53, a gene mutated in many spontaneous cancers. To determine if mutation of the Tp53 tumor suppressor gene plays a role in Abelson virus transformation, conformation-specific monoclonal antibodies were used to examine p53 expression in a panel of Abelson virus-transformed pre-B cells. Expression of mutant forms of p53 was detected in over 40% of the isolates. Sequence analysis revealed the presence of point mutations affecting the highly conserved central portion of the protein. These mutations interfered with the ability of p53 to activate transcription from a promoter containing p53-responsive elements and to induce apoptosis in response to DNA damage. In addition, cells expressing mutant forms of p53 induced a higher frequency of tumors with a more rapid course compared to transformants expressing wild-type p53. These data suggest that Tp53 is one important cellular gene involved in malignant transformation by Abelson virus.
 ...
PMID:Mutation of Tp53 contributes to the malignant phenotype of Abelson virus-transformed lymphoid cells. 934 65

One characteristic of B cells that accumulate during chronic lymphocytic leukemia (CLL) is their highly heterogeneous functional responses to B cell receptor (BCR) stimulation. Leukemic B cells with very poor responses have defective rapid tyrosine phosphorylation of numerous substrates, especially phospholipase C (PLC)gamma, as well as a defective calcium elevation on BCR stimulation. This points to a defect in BCR-associated protein tyrosine kinase (PTK). We investigated whether a defect in Syk, a PTK that is pivotal in coupling BCR to downstream signaling events, could account for these alterations. Syk tyrosine phosphorylation triggered by BCR ligation was severely impaired in B-CLL cells with low calcium responses to anti-mu stimulation. Syk associations were also defective, as concomitant tyrosine phosphorylation of a Syk-associated 145 kDa protein comigrating with PLCgamma-2 was only detected in responding B-CLL cells. By contrast, we found similar expression of the kinase regardless of B-CLL cell responsiveness. These results are consistent with the possibility that very proximal BCR signaling elements in some B-CLL cells are unable to connect with downstream biochemical events dominated by tyrosine phosphorylation and the potential docking function of Syk PTK.
Leukemia 1997 Nov
PMID:Normal Syk protein level but abnormal tyrosine phosphorylation in B-CLL cells. 936 27

The lymphoid-specific protein tyrosine kinase, p56lck which is essential for both T cell development and function, is aberrantly expressed in colon and small lung carcinoma lines. In this paper, we demonstrate p56lck is also expressed in colon tumour biopsies due predominantly or exclusively to the use of the lck type I promoter. In T leukaemia lines, the lck type I promoter requires binding sites for both Ets- and Myb-related transcription factors. In contrast, in colon tumour lines the activation of the lck type I promoter requires the Ets but not the Myb binding site. In these lines, a consensus binding site for HMG-related transcription factors, AACAAAG, is required for efficient lck type I promoter activity. Sox-4 is a candidate transcription factor for binding and activating the lck type l promoter in colon carcinoma cells. Co-expression of Ets-1 and Sox-4, but neither protein alone, was sufficient to activate the lck type l promoter in HeLa cells which do not normally express lck transcripts. These results suggest that aberrant expression of p56lck from the lck type l promoter in colon carcinoma arises from transcriptional activation mediated by Ets- and HMG-related transcription factors.
 ...
PMID:An alternative pathway for expression of p56lck from type I promoter transcripts in colon carcinoma. 941 36

Thy-1, a glycosyl-phosphatidylinositol-anchored surface glycoprotein, has been shown to possess transmembrane signaling capacity. In rat mast cells and rat basophilic leukemia cells (RBL) aggregation of surface Thy-1 with antibodies triggers a series of intracellular events, resembling those induced by aggregation of the high-affinity receptor for IgE (Fc epsilonRI), including tyrosine phosphorylation of multiple proteins and release of secretory components. Unlike the Fc epsilonRI-mediated activation, where both the membrane-associated protein tyrosine kinase (PTK) Lyn and the cytoplasmic PTK Syk are responsible for initiating the signaling cascade, only Lyn has been implicated in Thy-1-mediated activation in RBL cells. Here we report that Syk is also rapidly tyrosine phosphorylated upon Thy-1 cross-linking. Increased Syk tyrosine phosphorylation is observed only in cells in which extensive aggregation of Thy-1 is induced by two layers of cross-linking reagents. RBL-derived mutant cells deficient in the expression of surface Thy-1 and transfectants re-expressing surface Thy-1 were used to exclude the possibility that Syk activation reflects an interaction of the cross-linking reagents with surface molecules other than Thy-1. As Fc epsilonRI gamma subunits are well known to promote activation of Syk and its recruitment to membrane complexes, we also investigated the role of these subunits in Thy-1-mediated Syk activation, using RBL-derived mutant cells deficient in the expression of Fc epsilonRI gamma subunits and their revertants. Consistent with the lack of Fc epsilonRI expression, no IgE-induced response could be elicited, while Thy-1-inducible Syk phosphorylation was preserved. Our results suggest that Syk might be one of the kinases responsible for signal propagation upon Thy-1 cross-linking in a Fc epsilonRI-independent pathway.
 ...
PMID:Protein tyrosine kinase Syk is involved in Thy-1 signaling in rat basophilic leukemia cells. 946 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>