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)

Ditercalinium (DIT; NSC 335153), a 7H-pyridocarbazole dimer, was reported to be capable of binding with high affinity to DNA by bisintercalation. Both the cytostatic and cytotoxic effects of this drug have been attributed to its binding to DNA. DIT inhibits the growth and is cytotoxic to Friend erythroleukemia (FL) cells. When FL cells were treated with 0.5-2.5 microM DIT and then stained with acridine orange (AO), which differentially stains DNA and RNA, the green, orthochromatic fluorescence representing AO binding to DNA was unchanged, while the metachromatic red luminescence characteristic of AO binding to RNA was reduced by as much as 40% in 4 hr; the effect was DIT-concentration dependent. The reduction in RNA stainability by DIT in the absence of any significant decrease in RNA content, was also observed with another RNA-specific fluorochrome, pyronin Y (PY). These results indicate that in live cells DIT preferentially binds to RNA rather than DNA, preventing stainability of the former by the monointercalating dyes AO and PY. When FL cells were exposed to 10 microM DIT after being first permeabilized by ethanol, the subsequent stainability of DNA in these cells was reduced by up to 67% and RNA by up to 44%, indicating that under these conditions DIT binds to both DNA and RNA. This observation was confirmed by competition experiments between AO and DIT bound to DNA or RNA in permeabilized cells mixed with equivalent numbers of RNA-containing (DNase-treated) or DNA-containing (RNase-treated) cells, respectively. The mechanisms that protect DNA against binding by DIT in live cells are unknown but are lost in fixed cells and may be related to maintenance of cellular and/or nuclear membrane integrity. If the propensity for other intercalating drugs to bind to RNA in live cells is correlated with their antitumor activity as is DIT, the rationale for designing new drugs based solely on their affinity for DNA should be reevaluated.
Leukemia 1989 Jul
PMID:The antitumor intercalating drug ditercalinium binds preferentially to RNA in Friend erythroleukemia cells. 247 3

Serum ribonuclease (RNase) activity and its isoenzymes were determined by biochemical and PAGE electrophoretic separation technique in 20 patients with pancreatic cancer, in 27 with other gastroenterologic malignant tumors, 8 with acute pancreatitis, 7 with chronic pancreatitis, 5 with leukemia, 3 with chronic uremia of glomerulonephritis, and in 30 adult normal controls. Serum A1AT rocket immunoelectrophoresis and carcinoembryonic antigen (CEA) radioimmunoassay were also carried out simultaneously.
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PMID:Serum ribonuclease and its isoenzymes for diagnosis of pancreatic cancer. 250 4

Tumor necrosis factor (TNF) is a Mr 17,000 cytokine produced by macrophages. We have recently demonstrated that TNF is also produced by transformed human epithelial cells. The present studies have examined TNF expression in human myeloid leukemic cells. We have monitored TNF expression at a cellular level using alkaline phosphatase detection of a biotinylated TNF cDNA probe in situ. Using this approach, TNF transcripts were detectable in HL-60 cells induced along the monocytic lineage by phorbol ester but not in uninduced cells. The specific detection of TNF RNA at a cellular level was supported by the absence of histochemical staining in RNase-treated cells and when using biotinylated pBR322 plasmid without insert. These studies were extended to preparations of purified acute myeloblastic leukemia cells. The results demonstrate that TNF is expressed in myeloblasts in eight of nine patients with AML. In each preparation of myeloblasts with detectable TNF RNA, transcripts were present at 89-98% of the cells. The identification of TNF RNA in situ was also associated with the detection of TNF protein in leukemic blasts by indirect immunofluorescence. Moreover, the detection of TNF protein in these preparations of myeloblasts was confirmed by immunoblotting. However, using this approach to examine AML cells before and after purification indicated that TNF expression is induced as a result of the enrichment procedures. Thus, certain populations of purified myeloid leukemic cells are capable of expressing TNF at both the RNA and protein levels.
Leukemia 1989 Jan
PMID:Detection of tumor necrosis factor gene expression at a cellular level in human acute myeloid leukemias. 264 77

Mouse leukemia (P388) cells were incubated in cell culture medium containing nitrogen mustard [2-chloro-N-(2-chloroethyl)-N-methylethanamine] for 4 h. The nucleophosmin immunoband with a molecular weight of 37,000 (p37; other molecular weights are similarly designated) was observed in both control and nitrogen mustard-treated cells. Three additional immunobands with molecular weights of 80,000 (p80), 120,000 (p120), and 230,000 (p230) were identified in the drug-treated cells. The same results were observed with melphalan, but were not detected when mitomycin C, cis-platinum, Adriamycin, or actinomycin D were used. Treatments with DNase and RNase did not alter the molecular weights of these immunobands. These results indicate that the cross-linked products of nucleophosmin were not linked to DNA or RNA. The pI of p80, p120, and p230 is 5.1, which is the same as that of nucleophosmin (p37). The iodinated tryptic peptide map of p80 is identical to that of nucleophosmin. This result indicates that p80 is a dimer cross-linked by nitrogen mustard. The p80 and p120 immunobands were observed in Novikoff hepatoma and in hypertrophic rat liver, but were not detected in normal liver under the same conditions. These results indicate that tumor or proliferating cells have hexameric nucleophosmins which can be cross-linked by nitrogen mustards.
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PMID:Cross-linkage of nucleophosmin in tumor cells by nitrogen mustard. 272 Jun 80

p56lck, a member of the src family of cytoplasmic tyrosine protein kinases, is expressed primarily in lymphoid cells. Previous RNase protection data demonstrated the existence of at least two lck mRNAs (type I and type II) with different 5' untranslated regions in most T cells. These have been found here to arise from two separate promoters. S1 nuclease analysis and primer extension were used to locate the site of initiation of type I lck mRNA. The nucleotide sequence of the region upstream of this start site contains no classical promoter motifs. A cDNA clone of type II lck mRNA was isolated. The promoter of this mRNA must be more than 10 kilobases upstream of the type I promoter region. In two murine thymoma cell lines, LSTRA and Thy19, lck is expressed at elevated levels as a result of Moloney murine leukemia virus retrovirus promoter insertion. p56lck is encoded in these cells by a hybrid virus-lck mRNA containing the 5' untranslated region of Moloney virus mRNA. The structures and the sites of integration of the proviruses upstream of lck in these cells were examined by molecular cloning and Southern analysis. A truncated and rearranged provirus, flanked by 554 nucleotides (nt) of duplicated cellular sequences, was found 962 nt upstream of the start site for type I lck mRNA in LSTRA cells. What appears to be a Moloney mink cytopathic focus-forming provirus was found between 584 to 794 nt upstream of the start site for type I lck mRNA in Thy19 cells. Thus in both tumor cell lines, viral DNA is present between the promoters for type I and type II lck mRNAs. Comparison of the sequences of the 5' ends of the lck and c-src genes suggests that divergence of these two genes involved exon shuffling and that a homolog of the neuronal c-src(+) exon is not present in lck.
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PMID:Transcriptional activation of lck by retrovirus promoter insertion between two lymphoid-specific promoters. 284 26

The high-affinity IgE receptor present on mast cells and basophils is responsible for the IgE-mediated activation of these cells. The current model for this receptor depicts a four-subunit structure, alpha beta gamma 2. A cDNA for the alpha subunit was recently cloned and predicts a structure consisting of two homologous extracellular domains, a transmembrane segment, and a cytoplasmic tail. Using a synthetic oligonucleotide corresponding to the amino-terminal sequence of the alpha subunit, we identified a number of cDNA clones from a rat basophilic leukemia cell cDNA library. Nucleotide sequencing established four different forms of cDNA: one is nearly identical to the published cDNA; the second differs from the first in the 5' untranslated sequence; the other two forms use either one or the other of the 5'-end sequences as above and lack 163 base pairs in the region coding for the second extracellular domain. RNase protection analysis with radioactive RNA probes established the heterogeneity of rat basophilic leukemia cell mRNA with regard to both the 5' and the internal sequences. Our results suggest the existence of at least four different protein forms related to the alpha subunit of the high-affinity IgE receptor.
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PMID:cDNA heterogeneity suggests structural variants related to the high-affinity IgE receptor. 296 94

Poly ADP-ribosylation of two mouse lymphoma cell lines, L5178Y (LS) and the radiation and alkylating agent resistant derivative AII, was investigated by uptake of [3H]NAD by permeabilised cells into acid-precipitable material that was sensitive to phosphodiesterase but insensitive to DNase and RNase. Basal activities in both lymphoma lines were 3-4-fold greater than in mouse L1210 leukaemia cells. However, total endogenous poly (ADP-R) polymerase activity in both L5178Y cell lines, stimulated by a large excess of DNase in the presence of Triton X-100, was less than half the activity in L1210 cells. Doses of N-methyl-N-nitrosourea (MNU) that produced 20-50% survival of colony-forming units increased poly (ADP-R) in both lymphoma lines by only 25% compared with 377% in L1210 cells when synthesis was measured immediately after a 30-min exposure of MNU. During the first 24 h after MNU AII cells produced a peak of activity that was not seen with LS cells. A second peak was seen in both cell lines between 24 and 48 h following MNU. Concentrations of 3-aminobenzamide (3AB) above 2.5 mM inhibited colony-forming ability of lymphoma cells and equally inhibited uptake of [14C]formate into protein, RNA and DNA indicating that 3AB behaves as a general metabolic poison. Concentrations of 3AB in the toxic range of 3-10 mM inhibited poly (ADP-R) synthesis but no degradation of the polymer was observed. Non-toxic concentrations of 3AB potentiated cell killing by MNU to a similar degree in both lymphoma cell lines. In conclusion, we have found little evidence to support the hypothesis that the differential sensitivity of LS and AII is related to poly ADP-ribosylation. Compared with other mouse cells, L5178Y cells appear deficient in poly (ADP-R) polymerase and poly (ADP-R) glycohydrolase activities.
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PMID:Poly (ADP-ribose) metabolism in alkylated mouse L5178Y cells. 299 Jul 53

The major consequence of the formation of the Philadelphia (Ph1) chromosome characteristic of leukemia cells of patients with chronic myelogenous leukemia (CML) is fusion of c-abl and bcr genes. Using a sensitive RNase protection technique, we analyzed mRNA from a large number of CML patients. In most, we identified one or both species of bcr-abl chimeric transcripts. These two mRNAs vary in the specific bcr exon joined to abl exon II and are translated into slightly different proteins. The amounts of the fused mRNA within leukemia cells vary considerably between individuals and do not correlate with the phase of the disease.
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PMID:bcr-abl RNA in patients with chronic myelogenous leukemia. 310 69

DNA, RNA, and/or protein cellular content were studied by flow cytometry in 52 cases of acute myeloid leukemia before and on day 4 of remission induction treatment. Bone marrow (BM) samples were stained after fixation by acridine orange for DNA and RNA content (37 cases) and by propidium iodide and fluorescein isothiocyanate for DNA and protein content (52 cases). A positive correlation was found between pretreatment protein content and BM blast involvement: the higher the percentage of blasts in BM smears the higher the mean protein content (p less than 0.05). Protein content was higher in monoblastic leukemia (M4 and M5) than in the granulocytic types (M1, M2, M3) (p less than 0.05). S + G2 + M was higher in patients with protein content below 80 arbitrary units than in the subgroup with protein content above this threshold (p less than 0.05). Pretreatment RNA content, estimated by the RNase-sensitive fraction of G1 cells, was significantly higher in undifferentiated and M1 leukemias than in the other cytological groups (p less than 0.0001). This fraction was higher in patients who subsequently achieved complete remission, but it was not related to BM blast involvement or proliferative fraction of cells. During cytostatic treatment the changes in RNA and protein content did not follow a typical pattern. The connections between variations of DNA, RNA, and protein content and prognosis are examined and their possible relation to drug-induced blast cell maturation is discussed.
Leukemia 1988 Aug
PMID:DNA, RNA, and protein content in adult acute myeloid leukemia: effects of cytostatic drugs in vivo. 316 79

p56lck is a new member of the src family of cellular tyrosine protein kinases. It is expressed constitutively at a low level in normal T cells and at an elevated level in the LSTRA and Thy19 Moloney murine leukemia virus-induced thymoma cell lines. It is possible that the expression of p56lck at an elevated level contributes to the transformation of these thymoma cells. The structure of the mRNAs encoding p56lck was examined by using an RNase protection assay. Both a chimeric lck mRNA containing the 5' untranslated region of Moloney virus mRNA and a normal lck mRNA were found in Thy19 and LSTRA cells. The chimeric lck transcript was 4- to 10-fold more abundant than the normal transcript. Transcription arising from a viral promoter is therefore responsible for the elevated levels of lck mRNA in these two cell lines. Surprisingly, uninfected murine T cells were also found to contain lck transcripts with differing 5' untranslated regions. One species of mRNA was colinear with the region of the chromosome just upstream of the initiation codon for p56lck. The other appeared to arise through splicing of an unidentified 5' untranslated exon to a sometimes cryptic splice acceptor just upstream of the region encoding p56lck. These data suggest that lck is expressed through the use of at least two different promoters. The promoters could be subject to different forms of regulation.
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PMID:Two lck transcripts containing different 5' untranslated regions are present in T cells. 350 24


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