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)

The nonpathogenic human defective parvovirus adeno-associated virus (AAV) type 2 induced differentiation-associated antigens in cells of the human leukemia cell line HL60 (CD 67), as well as in two different lines of immortalized human keratinocytes, HaCaT and HPK Ia cells (involucrin and cytokeratin 10). Simultaneously, expression of the c-myc and c-myb oncogenes and the retinoblastoma gene was down regulated whereas c-fos expression increased in infected cells. These data point to the potential of AAV to induce functions related to the differentiation pathway in different types of human cells. This phenomenon may be involved in the reported oncosuppressive properties of AAV infections.
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PMID:Induction of differentiation-associated changes in established human cells by infection with adeno-associated virus type 2. 131

The BCR/ABL oncogene in chronic myelogenous leukemia produces an activated tyrosine kinase fusion protein (p210). Like other tyrosine kinase oncogenes, BCR/ABL can abrogate the interleukin-3 (IL-3) dependence of lymphoid cell lines. To investigate the ability of BCR/ABL to generate growth factor independence in myeloid cells, the IL-3 dependent myeloid cell line NFS/N1.H7 (H7) was transfected with the p210BCR/ABL-containing plasmid, pGD210. Stable clones A54 and A74 were capable of IL-3 independent growth and tumor formation in syngeneic mice. Relief of growth factor dependence was not mediated by autocrine release of IL-3. The baseline proliferation rate of the BCR/ABL transformed cells was greater than that of the parental H7 cells maximally stimulated by IL-3. Abundant constitutive expression of c-myc, c-jun, and c-fos was observed in the p210BCR/ABL transfectants even in low serum conditions. In contrast, c-myc expression in H7 cells was dependent upon IL-3 stimulation, and neither c-jun nor c-fos was highly expressed following IL-3 stimulation in H7 cells. Thus, BCR/ABL transformation and relief of IL-3 dependence involve not only pathways that can substitute for IL-3 induced growth via tyrosine kinase mediated signals, but also pathways that recruit constitutive c-jun and c-fos expression.
Leukemia 1992 Aug
PMID:BCR/ABL confers growth factor independence upon a murine myeloid cell line. 137 13

The v-abl oncogene of Abelson murine leukemia virus (A-MuLV) induces two opposite phenotypes in NIH3T3 cells. In the majority of cells, v-abl causes a growth arrest at the G1 phase of the cell cycle; while in a minority of cells, v-abl abrogates the requirement for growth factors. Using temperature sensitive mutants, it can be demonstrated that v-Abl tyrosine kinase is required for growth inhibition or stimulation. The two phenotypes are not caused by mutations or differences in the expression of v-Abl, but are dependent on the cell context. Two stable subclones of NIH3T3 cells have been isolated that exhibit similar morphology and growth characteristics. However, upon infection with A-MuLV, the 'positive' cells become serum- and anchorage-independent, whereas the 'negative' cells become arrested in G1. The positive phenotype is dominant, shown by cell fusion, and treatment with 5-azacytidine converts the negative cells to the positive phenotype. Activation of v-Abl tyrosine kinase induces the serum-responsive genes in the positive but not in the negative cells. Transactivation of the c-fos promoter by v-Abl in transient assays is also restricted to the positive cells. These results show that v-Abl tyrosine kinase is not an obligatory activator of growth, but requires a permissive cellular context to manifest its mitogenic function.
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PMID:Oncogenic v-Abl tyrosine kinase can inhibit or stimulate growth, depending on the cell context. 139 87

The present work has examined the effects of okadaic acid, an inhibitor of type 1 and 2A protein phosphatases, on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells. The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by: (a) growth arrest; (b) increases in Mac-1 cell surface antigen expression; (c) down-regulation of c-myc transcripts; and (d) induction of tumor necrosis factor gene expression. This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels, which were maximal at 6 h. Similar effects were obtained for the c-fos gene. Run-on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure. c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide, whereas inhibition of protein synthesis had little, if any, effect on okadaic acid-induced c-jun transcription. The half-life of c-jun mRNA was similar (45-50 min) in both untreated and okadaic acid-induced cells. In contrast, treatment with both okadaic acid and cycloheximide was associated with stabilization (t 1/2 = 90 min) of c-jun transcripts. Taken together, these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism. Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1, we also studied transcription of c-jun promoter (positions -132/+170)-reporter gene constructs with and without a mutated AP-1 element.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid. 141 3

Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is a transcriptional activator for viral gene expression and is also a transforming protein through inducing the expression of several cellular genes under the control of mitogenic signals. We identified the CArG boxes as a Tax1-responsive cis-acting element for the cellular immediate early genes c-fos, egr-1, and egr-2. Using a chimeric protein consisting of the CArG-binding factor p67SRF and the heterologous DNA-binding domain of a yeast transcription factor GAL4, we demonstrated that Tax1 activates the transcriptional activity of p67SRF through the GAL4-binding site. The carboxy-terminal half of p67SRF, which lacks domains for DNA-binding, dimerization, and ternary complex formation with p62TCF, was sufficient for the activation by Tax1. Tax1 produced in Escherichia coli bound p67SRF in vitro. The complex formation in vivo was also indicated by the finding that the acidic activation domain of VP16, by fusion to p67SRF, can complement the transcriptional activation function of a mutant Tax1 in trans. Thus, Tax1 activates CArG-mediated transcription without mitogenic signals through interaction with a CArG-binding factor, p67SRF. This must be one of the primary steps by which Tax1 causes aberration in growth control of the infected cells.
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PMID:Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes. 142 72

To study the signal transduction pathway leading to phorbol 12-myristate 13-acetate (PMA)-induced differentiation in human promyelocytic HL-60 leukemia cells, we examined the expression of protein kinase C (PKC) isozyme genes in HL-60 cells that are susceptible or resistant to PMA-induced differentiation. The PKC-alpha, -beta, -gamma, -delta, epsilon, and -zeta transcript levels were assessed by Northern blotting, and the PKC-alpha, -beta, and -gamma protein levels were examined by immunoblotting. The PMA-resistant cell variants HL-525 and HL-534 were found to be deficient in the PKC-beta isozyme RNA and protein as compared with the PMA-susceptible HL-60 and HL-205 cell lines. In addition, a "delta-like" PKC RNA species identified in these cells demonstrated a reduced abundance in the HL-525 and HL-534 cells. Southern blot analysis indicated that the observed reduction in PKC-beta gene expression does not appear to be due to a gross deletion or rearrangement of the gene. The expression of the early response genes junB, c-fos, and c-jun was attenuated in PMA-treated HL-525 and HL-534 cells as compared to the PMA-treated HL-60 and HL-205 cells. These results suggest that the signal transduction pathway that leads to PMA-induced differentiation in the HL-60 cell system requires PKC-beta and/or delta-like PKC for the proper expression of the early response genes, and ultimately the expression of genes that define the mature state.
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PMID:Protein kinase C beta gene expression is associated with susceptibility of human promyelocytic leukemia cells to phorbol ester-induced differentiation. 144 3

Chemically induced differentiation of Friend murine erythroleukemia cells (F-MELC) is a multistep process with a latent period of about 12 h preceding irreversible commitment to terminal maturation. To gain understanding of the early genetic response of F-MELC to the dimethyl sulfoxide (DMSO) inducer of F-MELC differentiation, we have investigated by Northern blot analysis the expression of fos and jun family genes that encode components of the transcription factor AP-1 complex. Our results show that c-jun mRNA is not detected at any time in untreated and DMSO-treated F-MELC. In contrast, DMSO-induced differentiation of F-MELC is associated with an early and transient induction of c-fos and junB mRNAs by 2 to 8 h treatment while in presence of dexamethasone, an inhibitor of F-MELC commitment, c-fos mRNA is not detected and junB mRNA remains at basal levels. junD mRNA is detected at low levels in untreated F-MELC and remains unchanged during DMSO treatment. Furthermore, DMSO treatment in a F-MELC cell line resistant to DMSO-differentiation does not result in an early induction of c-fos and junB mRNAs. Taken together, these results indicate that the DMSO-induced F-MELC differentiation is accompanied by an early co-induction of c-fos and junB during the latent period preceding the commitment to erythroid maturation.
Leukemia 1992 Sep
PMID:Co-induction of c-fos and junB during the latent period preceding commitment of Friend erythroleukemia cells to differentiation. 151 4

We examined the distribution of calpains I and II in human hematopoietic system cell lines by Western and Northern blot analyses and enzyme activity assay. Expression of calpain I, a low Ca(2+)-requiring cysteine protease, was observed in all human T-cell lines tested. By contrast, expression of calpain II, a high Ca(2+)-requiring form, in human T-cells was closely correlated with human T-cell leukemia virus type I (HTLV-I) infection, which is known to result in the expression of adult T-cell leukemia-associated antigens, interleukin-2 (IL-2) receptor alpha, and Ca(2+)-dependent cell proliferation. Specific expression of calpain II in HTLV-I-infected cells occurred at the mRNA level. Furthermore, expression of calpain II in human natural killer-like cells was augmented by HTLV-I pX gene transfection. In HTLV-I-infected cells, the trans-acting transcriptional activation of the long terminal repeat and control elements for the IL-2 receptor alpha, c-fos, and granulocyte-macrophage colony-stimulating factor genes by the Tax from the pX gene is already known. Our results suggest that the similar trans-activation occurs to the calpain II gene in HTLV-I-infected hematopoietic system cells.
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PMID:Expression of calpain II gene in human hematopoietic system cells infected with human T-cell leukemia virus type I. 152 57

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

Approaches to analysing gene regulation in haematopoietic stem cells are limited by their low concentration and rapid cell death outside of a trophic marrow environment. We have used interleukin 3 (IL3)-dependent cell lines as stem-cell models to investigate gene regulation during signal transduction by growth factors. We report that expression of the bacterial chloramphenicol acetyl transferase reporter gene linked via the weak thymidine kinase promoter to known upstream enhancer regions required for expression of the proliferation-dependent proto-oncogene c-fos occurs almost immediately (within 2 h) after transfection. Expression is stimulated by IL3 or activation of protein kinase C. Our findings indicate that IL3-dependent cell lines possess an extremely rapid transcription mechanism for introduced DNA, which if also present in normal cells may be usefully used to analyse gene regulation during signal transduction leading to growth and differentiation by haematopoietic growth factors.
Leukemia 1992 Jul
PMID:Haematopoietic stem cell lines activate novel enhancer-dependent expression of reporter DNA immediately after transfection by mechanisms involving interleukin 3 and protein kinase C. 162 95


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