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

We investigated the expression, degree of phosphorylation, and activation of the proto-oncogene c-kit product before and after stimulation with the c-kit ligand in a human factor-dependent myeloid leukemia cell line, MO7E. The culture supernatant of the BALB/3T3 fibroblast cell line, which contains the ligand for the murine c-kit product, was found to stimulate proliferation of the MO7E cell line in a dose-dependent manner. The proliferation was significantly inhibited by a tyrosine kinase inhibitor, genistein. An immunoblot technique with a monoclonal antibody specific for phosphotyrosine, showed that there was rapid, dose-dependent tyrosine-phosphorylation of the c-kit product in response to murine c-kit ligand. Furthermore, the murine c-kit ligand increased autokinase activity of the c-kit product in vitro. Similar results were obtained with human stem cell factor (SCF), a recombinant human ligand for the c-kit product. These results suggest that the phosphorylation and activation of the c-kit product are involved in proliferative signals of some human leukemia cells, as well as of normal hematopoietic cells.
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PMID:Proliferation of human myeloid leukemia cell line associated with the tyrosine-phosphorylation and activation of the proto-oncogene c-kit product. 172 36

The in vitro proliferation of the spontaneous lymphoid T-cell leukemia designated LB was enhanced by physiological, intermediate and supraphysiological concentrations of insulin. The enhancing effect was observed in both serum-free medium (SFM) and medium containing low concentrations of serum. Guinea-pig anti-insulin serum, but not guinea-pig normal serum, inhibited the proliferation of LB cells incubated either in medium containing serum alone or in medium containing serum and supplemented with insulin. This finding suggests that LB cells use serum insulin as a growth factor. Insulin-like growth factors I (IGF-I) and II (IGF-II) failed to stimulate an appreciable proliferation in LB cells, whereas in the same experiment insulin markedly enhanced the proliferation of this lymphoid leukemia. Furthermore, the concentration of unlabelled insulin required to displace 50% of 125I-insulin bound to LB cells was 3 orders of magnitude lower than the concentration of IGF-I required to achieve the same displacement. Our findings indicate that interaction of insulin with its own receptor, and not with IGF-I receptor, triggers the proliferation of LB cells. Radio-receptor assays revealed that LB cells express approximately 3,200 molecules of high affinity (Kd = 10(-9) M) insulin receptor per cell. None of 7 other tumor cell lines tested responded to insulin. The proliferation of insulin-stimulated LB cells was also inhibited with tyrphostin, a tyrosine kinase blocker analogous to tyrosine, which perhaps blocks the tyrosine kinase activity of the insulin receptor beta-chain.
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PMID:Insulin dependence of murine lymphoid T-cell leukemia. 172 17

The cellular gene c-abl is the normal homologue of the transforming gene (v-abl) within the genome of the Abelson leukaemia virus. The cDNA sequence coding for the cellular form of the murine abl gene (c-abl type IV) has been inserted into the baculovirus transfer vector, pAc36C, so that the c-abl gene is under the control of the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV). Spodoptera frugiperda cells infected with the recombinant transfer vector in the presence of wild type AcNPV DNA yielded recombinant, polyhedrin negative virus that expressed moderate levels of the c-Abl protein (representing approx. 0.5-1% of the stained cellular proteins as determined by densitometric scanning). The insect derived c-Abl protein was compared to the P210-BCR/ABL protein from K562 cells, a cell line derived from a patient with chronic myelogenous leukaemia. Antibodies raised against synthetic peptides based on c-abl encoded peptides react with the insect derived c-Abl. In addition, the baculovirus derived c-Abl protein has a tyrosine kinase activity as demonstrated by phosphorylation of a synthetic polypeptide and also by autophosphorylation. Phosphoamino acid analysis of immunoprecipitated, autophosphorylated baculovirus derived c-Abl protein indicates that the majority of label incorporated is on the tyrosine residues. Immunofluorescence microscopy has been used to show that the majority of the c-Abl protein expressed in cells infected with recombinant virus is located in the nuclear and plasma membranes.
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PMID:Expression of the mouse c-abl type IV proto-oncogene product in the insect cell baculovirus system. 173 71

Abnormalities of p53 mRNA in adult T-cell leukemia (ATL) were analyzed using reverse transcription-polymerase chain reaction-single strand conformation polymorphism analysis. Mutations were present in two of 12 ATL patients studied, but not in 3 cell lines immortalized by human T cell leukemia virus type 1 (HTLV-1) infection in vitro. Direct sequencing analysis of the p53 gene from these two patients revealed missense point mutations at codon 153 (arginine to histidine) or codon 220 (cysteine to tyrosine), respectively. Immunohistochemical analysis revealed the elevated expression of p53 proteins in ATL cells from a patient carrying the mutated p53 gene at codon 158. Neither gross rearrangement of p53 gene nor abnormal size of mRNA for the gene was demonstrated by Southern or Northern blot analyses. Thus, there is a mutated p53 in some patients with ATL. The involvement of abnormalities in some suppressor oncogenes may play a role in the development of ATL.
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PMID:Genetic alteration of p53 in some patients with adult T-cell leukemia. 177 65

Two bcr/abl fusion gene products with tyrosine kinase activity have been found in two phenotypes of Philadelphia chromosome (Ph1)-positive leukemia. P210bcr/abl (P210) is associated with Ph1-positive chronic myelogenous leukemia (CML), while P190bcr/abl is associated with Ph1-positive acute leukemia. We compared the susceptibility of 32Pi-labeled P210 from K-562 cells and P190 from MR-87 cells to protein tyrosine phosphatase (PTPase). PTPase, present in the lysate of mature granulocytes from CML patients as well as in the lysate of these cells from normal subjects, effectively dephosphorylated the CML-associated P210 and the acute leukemia associated P190. This PTPase activity was specifically inhibited by ZnCl2; it was not present in lymphocyte lysates, and was not inhibited by neutralization with anti-CD45 antibody. Since P210 and P190 were equally sensitive to the PTPase, the difference in leukemic phenotypes associated with the expression of these two tyrosine kinases cannot be explained by the differential dephosphorylation of P210 and P190.
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PMID:Two bcr/abl fusion gene products, P210bcr/abl and P190bcr/abl, are equally sensitive to the protein tyrosine phosphatase of mature granulocytes. 179 29

Treatment of rat basophilic leukemia cells (RBL-2H3) with antigen or ionophore leads to an increase in cellular protein tyrosine phosphorylation. Three major proteins of molecular mass of 72, 92, and 110 kDa are targeted by antigen and a 110-kDa species by ionophore, A23187. The antigen- and ionophore-induced tyrosine phosphorylation responses are dose-dependent and correlate with increases in serotonin release from activated cells. The presence of extracellular Ca2+ is required to sustain the antigen- and ionophore-stimulated tyrosine phosphorylation as well as mediator release. A protein tyrosine kinase inhibitor, RG 50864, differentially inhibits the antigen-stimulated tyrosine phosphorylation in the decreasing order of 72, 91, and 110-kDa proteins. The compound inhibition of the 72-kDa protein tyrosine phosphorylation correlates with that of serotonin release. In ionophore-stimulated cells, the inhibition of the 110-kDa protein tyrosine phosphorylation and serotonin release by RG 50864 occurs in parallel. These results suggest that the 72- and 110-kDa phosphoproteins may represent the respective regulators of serotonin release in antigen- and ionophore-activated cells. The 110-kDa tyrosine phosphorylated proteins from antigen- and ionophore-stimulated cells exhibit identical electrophoretic mobility and V8 protease-generated phosphopeptide maps, suggesting that these two proteins may be the same. These results provide new evidence that both the stimulatory actions of antigen and ionophore on mediator release are mediated through enhanced protein tyrosine phosphorylation in RBL-2H3 cells. Significantly, the present study suggests the presence of multiple tyrosine phosphorylation signaling pathways in RBL cells and that their selective utility may be determined by the nature of the stimulus.
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PMID:Antigen- and ionophore-induced signal transduction in rat basophilic leukemia cells involves protein tyrosine phosphorylation. 183 74

Crosslinking HLA-DR molecules by monoclonal antibodies (mAb) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic Ca2+ concentration ([Ca2+]i) in activated human T cells. Here we have studied the effect of DR on CD3-induced signal transduction in allospecific T-cell clones and T-leukemia (HUT78) cells. Co-crosslinking of DR with CD3 produced an enhanced [Ca2+]i response compared to that seen with CD3 alone. In contrast, CD2 responses were not enhanced by co-crosslinking with DR. Co-crosslinking CD45 in a tri-molecular complex of CD45, CD3, and DR completely abrogated the enhancing effects of DR on CD3-induced [Ca2+]i responses. In contrast, the enhancing effect of co-crosslinking CD4 on CD3 responses was not inhibited by co-crosslinking CD45. Thus, the DR-mediated accessory signals appear to be regulated differently from those provided by CD4 accessory molecules. The present data confirm, at the level of second messengers, recent findings suggesting that DR molecules have accessory functions in CD3/Ti-mediated T-cell responses.
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PMID:HLA-DR molecules enhance signal transduction through the CD3/Ti complex in activated T cells. 183 88

The specificity of the p15 proteinase of myeloblastosis-associated virus (MAV) was tested with nonviral high molecular weight substrates and with synthetic peptides. Peptides with sequences spanning known cleavage sites in viral polyproteins of Rous sarcoma virus (RSV) and avian leukemia viruses, as well as in BSA and HSA, were synthesized, and the rate of their cleavage by the MAV proteinase was compared. Synthetic peptides require for successful cleavage at least 4 residues at the N-terminal side and 3 residues at the C-terminal side. The proteinase shows a preference for hydrophobic residues with bulky side chains (Met, Tyr, Phe) in P3, although Arg and Gln can also be accepted. Small hydrophobic residues are required in P2 and P2', and large hydrophobic residues (Tyr, Met, Phe/p-nitro-Phe) are preferred in both P1 and P1'. The difference between the specificity of the p15 proteinase and that of the HIV-1 proteinase mostly pertains to position P2' of the substrate, where bulkier side chains are accepted by the HIV-1 proteinase (Richards et al., 1990). A good chromogenic substrate for the MAV and RSV proteinases was developed and used to further characterize the MAV proteinase activity with respect to ionic strength and pH. The activity of the proteinase is strongly dependent on ionic strength and pH. Both the kcat and Km values contribute to a higher cleavage efficiency at higher salt concentrations and show a bell-shaped pH dependence curve with a sharp maximum at pH 5.5 (kcat) and 6.5 (Km).
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PMID:Specificity studies on retroviral proteinase from myeloblastosis-associated virus. 184 25

The CD45 antigen cluster identifies a family of transmembrane glycoprotein tyrosine phosphatases (PTPases) present on nearly all hemopoietic cells. Recent studies suggest that CD45 may play a role in the control of receptor mediated blood cell responses, and that expression of the CD45 gene varies during bone marrow cell maturation. However, relatively little is known of the mechanisms controlling CD45 expression and function. Here we show that the induction of granulocyte or monocyte differentiation of HL60 leukemia cells is accompanied by a rapid increase in CD45 antigen expression and CD45 PTPase activity. In contrast, other leukemia cell lines induced for monocyte/macrophage differentiation did not show increased CD45. Immunoprecipitation of radiolabelled CD45 glycoprotein from dimethyl sulphoxide (DMSO) treated HL60 cells indicated that the cells expressed 200 and 180 kD isoforms. Northern blots of steady-state RNA from HL60 cells showed a 4-11-fold increase in CD45 transcripts after DMSO treatment, but no alteration in the half-life of CD45 mRNA. Nuclear transcription assays showed that CD45 expression was controlled at the level of gene transcription. Namalwa Burkitt leukemia cells expressing the heterologous epidermal growth factor (EGF) receptor protein tyrosine kinase were used to assess the specificity of CD45 PTPase activity. Co-clustering of CD45 and the EGF receptor with specific monoclonal antibodies failed to alter the EGF stimulated tyrosine phosphorylation of the EGF receptor. These studies indicate that CD45 increases during myeloid maturation, and the expression of the CD45 gene is controlled at the level of gene transcription. Preliminary studies suggest that CD45 does not alter the protein tyrosine kinase activity of the EGF receptor in intact cells, suggesting substrate specificity in vivo.
Leukemia 1991 Apr
PMID:Regulation of CD45 expression in human leukemia cells. 185 Dec 41

Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), two multifunctional cytokines lacking structural homology and binding to distinct receptors, share interesting functional similarities, which include induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, and stimulation of acute-phase protein synthesis in hepatocytes. Structural information on the LIF receptor is not yet available, whereas recent cloning of the IL-6 receptor has shown it to be bipartite, with a signal-transducing subunit that lacks sequence homology to known protein kinases and produces second messengers of unknown nature. The molecular nature of the mechanisms which LIF and IL-6 use to induce cell differentiation is not known. To address this issue, we took advantage of a clone of M1 myeloblastic leukemia cells capable of being induced for terminal differentiation by both LIF and IL-6 directly activate the same set of immediate early response genes upon induction of M1 myeloid differentiation. At least two mechanisms of gene activation, one transcriptional and the other posttranscriptional, are shown to be involved. It is also shown that the LIF and IL-6 immediate early response, at suboptimal cytokine concentrations, is additive. Using a variety of protein kinase activators and inhibitors, we have shown that the intracellular signalling pathways for both LIF and IL-6 are distinct from those of known second messengers and involve protein phosphorylation, notably tyrosine phosphorylation of a 160-kDa protein, as an essential step(s) in the immediate early activation of MyD gene expression. These observations indicate that the functional similarities of LIF and IL-6 as inducers of cell differentiation prevail at the level of the complex differentiation immediate early response and implicate common mechanisms of signal transduction for LIF- and IL-6-induced differentiation.
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PMID:Leukemia inhibitory factor and interleukin-6 trigger the same immediate early response, including tyrosine phosphorylation, upon induction of myeloid leukemia differentiation. 190 51


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