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)

Cytogenetic and molecular studies were made in 4 patients with Ph negative chronic myelogenous leukemia (CML) and 4 patients with CML with unusual Ph translocation. Chromosome analysis was performed on direct preparations and short-term cultures of bone marrow cells by R and G bandings. Southern blot analysis of DNA from leukemia cells was made using 4.5kb bcr-u and 1.5kb bcr-HE probes. Four patients with Ph negative CML had normal karyotypes. Among them, 3 had rearrangement of bcr, and 1 expected germ line pattern only. In the 4 patients with CML with unusual Ph translocation who had bcr rearrangement, one had a masked Ph chromosome originating from a translocation t(3;22) (p22;q11), the other three had one of the following complex Ph translocations: t(9;22;13) (q34;q11;q21), t(3;14;22) (p21;q32;q11) and t(X;9;22;12) (q22; q34; q11; q24). Our data confirmed that Ph negative CML could be divided into two different subsets: Ph-bcr+ CML and Ph-bcr-CML and that whatever the type of translocation may be, CML with unusual Ph translocation and Ph positive CML had a common molecular pathological basis.
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PMID:[Cytogenetic and molecular studies in patients with chronic myelogenous leukemia without Ph chromosome and with unusual Ph translocation]. 839 13

The protein smg p21A/Krev-1/rap 1A was identified as a ras p21-like small G-protein, having the ability to revert v-Ki-ras transformed NIH 3T3 fibroblasts. The expression level of smg p21A and ras p21s during phorbol ester-induced differentiation of HL-60 and MEG-01 cell lines was analyzed by immuno- and Northern blotting. In both cell lines, levels of smg p21 and ras p21s increased quickly in early phase of differentiation along with the appearance of differentiation phenotypes. They increased 3-4 fold on days 1-2, then decreased gradually. The increasing smg 21 mRNA levels also corresponded with that of products. Among ras mRNAs, Ha-ras and N-ras transcripts increased somewhat faster than smg 21. These small G-proteins may play closely related roles in the differentiation of these leukemia cell lines.
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PMID:Up-regulation of small GTP-binding proteins smg P21A and ras P21S during TPA-induced differentiation of human leukemia cell lines. 842 89

Granulocytic leukemia was induced in Long-Evans (LE) rats by using the Huggins and Sugiyama method. After serial passage the cells became transformed. The newly transformed cells could be transplanted to LBF1 hybrid rats and observed more readily. A quantity of 10(8) cells/100 g body weight was injected intravenously and after 2-3 weeks myelomonocytic leukemia developed. By examining the bone marrow, spleen and lymph nodes, cytochemical tests verified this transformation. Transplanting 10(2)-10(4) cells under the renal capsule, a quickly growing solid tumor was observed, which caused metastasis to the parathymical lymph nodes and peritoneum. The investigation of oncogene expression for the myc and ras families revealed the presence of myc p62 and ras p21 oncoproteins in the tumor cells by using monoclonal antibodies in immunohistochemical tests. LBF1 rats proved to be good models in obtaining solid tumor growth and myelomonocytic leukemias, equivalent to human M4-M5 type leukemia.
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PMID:Studies on acute myelomonocytic leukemia in LBF1 rats. 844 91

Sera from a small sample of adult blood donors, healthy school children and patients with lymphoma, leukaemia, non-haematologic cancer, congenital and inflammatory disorders from Ibadan, Nigeria were screened for HTLV-I antibody by an enzyme-linked immunoabsorbent assay and confirmed by investigational Western blot. Seventy-nine of 236 positively screened samples could not be tested for confirmation. Seropositive reactivity was observed in nine of 123 blood donors, and 3 of 46 healthy school children but banding patterns on Western blot were often sparse. Among non-Burkitt's non Hodgkin's lymphoma patients six of 30 were HTLV-I positive including four of four with clinical features of adult T-cell leukaemia (ATL). Other clinical conditions had a frequency of positivity indistinguishable from healthy donors. Western blot patterns ranged from strong with multiple bands, which were uncommon, to those with only p24 and p21 envelope positive which were frequent. Given the relative paucity of clinical ATL and the unusual Western blot patterns the true rate of HTLV-I infection may be lower than estimated. It is possible that a cross-reactive HTLV-I-like virus accounts for this pattern.
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PMID:Frequency of adult T-cell leukaemia/lymphoma and HTLV-I in Ibadan, Nigeria. 847 36

Moloney murine leukemia virus causes thymic leukemias when injected into newborn mice. A major determinant of the thymic disease specificity of Moloney virus genetically maps to the conserved viral core motif in the Moloney virus enhancer. Point mutations introduced into the core site significantly shifted the disease specificity of the Moloney virus from thymic leukemia to erythroid leukemia (N.A. Speck, B. Renjifo, E. Golemis, T.N. Fredrickson, J.W. Hartley, and N. Hopkins, Genes Dev. 4:233-242, 1990). We previously reported the purification of core-binding factors (CBF) from calf thymus nuclei (S. Wang and N.A. Speck, Mol. Cell. Biol. 12:89-102, 1992). CBF binds to core sites in murine leukemia virus and T-cell receptor enhancers. Affinity-purified CBF contains multiple polypeptides. In this study, we sequenced five tryptic peptides from two of the bovine CBF proteins and isolated three cDNA clones from a mouse thymus cDNA library encoding three of the tryptic peptides from the bovine proteins. The cDNA clones, which we call CBF beta p22.0, CBF beta p21.5, and CBF beta p17.6, encode three highly related but distinct proteins with deduced molecular sizes of 22.0, 21.5, and 17.6 kDa that appear to be translated from multiply spliced mRNAs transcribed from the same gene. CBF beta p22.0, CBF beta p21.5, and CBF beta p17.6 do not by themselves bind the core site. However, CBF beta p22.0 and CBF beta p21.5 form a complex with DNA-binding CBF alpha subunits and as a result decrease the rate of dissociation of the CBF protein-DNA complex. Association of the CBF beta subunits does not extend the phosphate contacts in the binding site. We propose that CBF beta is a non-DNA-binding subunit of CBF and does not contact DNA directly.
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PMID:Cloning and characterization of subunits of the T-cell receptor and murine leukemia virus enhancer core-binding factor. 849 54

We have examined whether activation of MAP kinases [or extracellular signal-regulated kinases (ERKs)] is required for the survival of rat sympathetic neurons by comparing the actions of three survival factors whose survival-promoting actions can be blocked by neutralizing Fab fragments to p21 ras (Nobes and Tolkovsky, 1995, Eur. J. Neurosci., 7, 344-350), nerve growth factor (NGF), the cytokines ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF), and the cyclic AMP analogue 4-(8-chlorophenylthio)cAMP (CPTcAMP). NGF-induced survival was accompanied by an intense (15- to 30-fold) and steady (> 24 h) activation of p44 and p42 ERKs which waned rapidly (t1/2 approximately 30 min) upon NGF withdrawal. However, concentrations of NGF that induced a weak (4- to 5-fold) stimulation of the ERKs were not sufficient to maintain long-term survival. Moreover, prolonged and intense stimulation of the ERKs by NGF for up to 15.5 h was unable to confer long-term survival, since withdrawal of NGF after this time resulted in neuronal death that was kinetically indistinguishable from the death of neurons that had not been exposed to NGF. By contrast, CNTF and LIF continued to support survival for up to 3 days after eliciting only transient (< 30 min and 1 h respectively) activation of p44 and p42 ERKs, while CPTcAMP induced survival for several days without any measurable activation of the ERKs. Taken together, these data suggest that ERK activation per se is neither necessary nor sufficient for survival and that alternative pathways exist for effecting long-term survival of rat sympathetic neurons.
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PMID:Activation of p44 and p42 MAP kinases is not essential for the survival of rat sympathetic neurons. 854 72

The CDK-inhibitor p21WAF1/CIP1 has been implicated as a growth arrest mediator in p53-tumour suppression, cellular senescence and terminal differentiation. Cell type specific differences in p53-independent p21 expression and cell cycle arrest were found following treatment of human tumour cell lines with serum, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), or okadaic acid (OA). TPA induced p21 in ML1, K562 and HL60 leukemia cells, whereas OA induced p21 in SW480 and GM4723 carcinoma cells as well as in leukemic cells. In addition, TPA- and serum- but not OA-induced cell cycle arrest was reversed upon return of p21 to basal levels. To further investigate the mechanisms underlying p53-independent regulation of p21, the transcription inhibitor, Actinomycin D (AMD), was used to block p21 expression. The results showed a complete inhibition of p21 mRNA and protein induction by TPA or adriamycin but little effect on p21 mRNA induced by OA in the presence of AMD. These results suggested that TPA-induced p21 expression requires transcription initiation, while a post-transcriptional mechanism may be involved in OA-induction as well. Transient transfection assays with p21 promoter-luciferase reporters and TPA or OA treatment further confirmed that TPA, and to a lesser extent, OA, initiated transcription of p21. Finally, the protein kinase C inhibitor, staurosporine, was found to interfere with p21 induction and prevent cell cycle arrest following treatment with TPA but not OA, suggesting a requirement for PKC in TPA activation of p21 expression.
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PMID:Regulation of p21WAF1/CIP1 expression by p53-independent pathways. 862 72

Parental and multidrug resistant HL60 leukemia cell lines were used to study coupling of expression of apoptotic/cytostatic (bcl-2, bax, bclxL, p21/Waf1, and c-myc) genes during differentiation. The multidrug resistant HL60 cell line, HL60/ADR, was less sensitive than parental cells to cytostatic activity of low (0.4-2 ng/ml) doses of PMA. However, during treatment with standard differentiating doses of PMA (10 ng/ml), no difference between the two cell lines in cytostasis and differentiation was found. Downregulation of c-myc and upregulation of p21/Waf1 proteins showed the same time-course in both cell lines. The bcl-2 mRNA was rapidly downregulated while bax and bclxL gene expression was not altered in both differentiating HL60 and HL60/ADR cells. Significant downregulation of bcl-2 protein occurred only in parental HL60 cells. In HL60/ADR, despite rapid cessation of bcl-2 protein synthesis, almost no change in steady-state bcl-2 protein level was found. The lack of bcl-2 protein downregulation was a result of the prolonged half-life of this protein in HL60/ADR cells. Thus, although downregulation of bcl-2 mRNA is coupled to differentiation, actual loss of bcl-2 protein is not required for accomplishment of the differentiation program.
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PMID:bcl-2 protein downregulation is not required for differentiation of multidrug resistant HL60 leukemia cells. 862 7

1. We investigated the effect of Clostridium botulinum C3 ADP-ribosyltransferase upon beta-hexosaminidase release induced by various stimuli from streptolysin-O (0.5-1 U/ml)-permeabilized rat basophilic leukemia (RBL-2H3) cells. 2. The C3 transferase inhibited beta-hexosaminidase release induced by Ca2+ or by guanosine-5'-(3-thiotriphosphate) (GTP gamma S) plus Ca2+. 3. The C3 transferase also inhibited beta-hexosaminidase release induced by stimulating high affinity IgE and m3 muscarinic acetylcholine receptors. 4. The substrate for the C3 transferase was present in cytosol of RBL-2H3 cells, indicating the presence of rho p21. About 60% of the total cellular substrate protein remained within the cells permeabilized by 1 U/ml of streptolysin-O. 5. The protein rho p21 appears to be regulated by several pathways and it may function as an integration point for exocytosis.
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PMID:Regulation of exocytosis by the small GTP-binding protein Rho in rat basophilic leukemia (RBL-2H3) cells. 869 Feb 50

Towards dissecting the regulation of terminal differentiation, including growth arrest and apoptosis, myeloid differentiation primary response (MyD) genes, induced in the absence of de novo protein synthesis following induction of M1 myeloblastic leukemia cells for terminal differentiation have been isolated. MyD118 was one of the novel MyD genes cloned, subsequently observed also to be a primary response gene to TGF-beta, which induces M1 cells for growth arrest and apoptosis uncoupled from differentiation. The MyD118 encoded protein was observed to be remarkably similar to the protein encoded by Gadd45, a growth arrest and DNA damage induced gene, regulated in part by the tumor suppressor p53. Though evidence has accumulated that MyD118 functions as an important modulator of negative growth control both in hematopoietic and non-hematopoietic cells, its mechanism of action is unknown. To better understand the role(s) of MyD118 in negative growth control, we have analysed the expression and biological characteristics of the MyD118 protein, compared to the Gadd45 protein, in distinct pathways of growth arrest and apoptosis, including p53 dependent and independent pathways either coupled or uncoupled from differentiation. It is shown that MyD118 and Gadd45 differentially accumulated upon induction of distinct pathways of growth arrest and apoptosis; notably, MyD118, but not Gadd45, was induced by TGF-beta, whereas Gadd45, but not MyD118, was induced by activating wild type (wt) p53 function. It is also shown that MyD118 is a nuclear protein, which regardless of the pathway induced, predominantly localized within the cell nucleus, and interacted with the DNA replication and repair protein PCNA and the cyclin dependent kinase inhibitor P21WAF1/CIP1. MyD118 also modestly stimulated DNA repair in vitro. All of these characteristics were shared with Gadd45. Finally, it is demonstrated that MyD118, Gadd45 and p21 synergized in the suppression of colony formation by NIH3T3 cells. Taken together, these findings demonstrate that MyD118 and Gadd45 are representative of a new protein family that share remarkable functional similarities in the control of distinct pathways of negative growth, including the suppression of cellular growth and programmed cell death.
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PMID:The differentiation primary response gene MyD118, related to GADD45, encodes for a nuclear protein which interacts with PCNA and p21WAF1/CIP1. 870 May 17


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