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)

Recombination studies have established that retroviral long terminal repeats (LTRs) are important genetic determinants of the viral capacity to induce hematopoietic tumors and to specify the type of cell making up the tumor. Plasmids containing LTRs of several murine leukemia viruses linked to the chloramphenicol acetyltransferase gene were tested in transient assays to measure relative rates of transcriptional activity in different types of hematopoietic cells. LTRs of the thymomagenic viruses SL3-3, Moloney leukemia virus, and a Moloney mink cell focus-forming virus all expressed to higher levels than other LTRs in T-lymphocyte cell lines. Conversely, the LTRs of Friend leukemia virus and a polycythemic spleen focus-forming virus expressed to higher levels than other LTRs in erythroleukemia cells. The LTR of nonleukemogenic Akv virus induced a relatively low level of activity compared with the others in all cells tested. Thus the relative level of LTR-driven expression in various types of cells corresponds to the type of tumor caused by the intact virus in vivo. These results provide direct evidence that the tissue specificity of the transcriptional activity of LTRs plays a critical role in determining the target cell for retroviral oncogenesis.
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PMID:Correlation of leukemogenic potential of murine retroviruses with transcriptional tissue preference of the viral long terminal repeats. 302

The oligosaccharide-anthracyclines, aclacinomycin A, marcellomycin and musettamycin, are potent inducers of erythroid differentiation in hemopoietic cells lines of rodent and human origin. The present studies revealed that pyrromycin, a closely related monosaccharide-anthracycline, induced erythroid differentiation in Friend leukemia cells and in the human leukemia cell line K 562. Pyrromycin, marcellomycin and musettamycin, which possess an identical aglycone structure containing a Cl-hydroxyl group, exhibited relatively low optimal inductive concentrations. In contrast, the optimal inductive concentration of aclacinomycin A, which lacks the Cl-hydroxyl group, was markedly higher, i.e., the differentiation inducing capacity was lower. It should be noted, however, that the yield of differentiated cells following treatment with the monosaccharide-anthracycline pyrromycin was distinctly lower than that after treatment with the oligo-saccharide-anthracyclines, aclacinomycin A, marcellomycin or musettamycin. Thus, our data indicate that the efficacy of anthracyclines to induce erythroid differentiation is related to a) the presence of a Cl-hydroxyl group in the aglycone and b) the presence of an oligosaccharide side chain.
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PMID:Induction of erythroid differentiation by the anthracycline antitumor antibiotic pyrromycin. 322 6

Ditercalinium (NSC 335153) is a novel 7H-pyridocarbazole dimer in which the two monomers are joined by a rigid bis(ethylpiperidinyl)-linking chain producing a molecule capable of bisintercalation into DNA with extremely high affinity. The effect of ditercalinium on cell proliferation and its interaction with DNA in situ has been investigated in the Friend leukemia cell system. Ditercalinium caused an inhibition of cell growth at 0.5 microM and cell death at 2.5 microM. However, both the cytokinetic and cytotoxic effects became evident only after 1-2 days of continuous drug exposure. In contrast, monointercalators generally affect cell growth within several hours of administration. Furthermore, whereas most intercalators arrest cells in G2 phase, ditercalinium demonstrated no cell cycle phase specificity. In fact, a stathmokinetic experiment, in which vinblastine was used to prevent cell division in exponentially growing Friend leukemia cell cultures, demonstrated that ditercalinium effectively "froze" cells in position throughout the cell cycle, in a dose-dependent fashion. By determining the sensitivity of DNA in situ in fixed Friend leukemia cells to acid-induced denaturation, it was apparent that ditercalinium, rather than stabilizing DNA as do monointercalators, increased the sensitivity of DNA in situ to denaturation induced by acid. It appears, therefore, that the cytokinetic effects and interaction with chromatin of an agent that has the ability to bisintercalate into DNA are qualitatively different from those induced by classical monointercalating drugs.
Leukemia 1987 May
PMID:Cytokinetic effects of bifunctional antitumor intercalator ditercalinium on Friend erythroleukemia cells. 347 39

The N-B locus affecting tissue culture infectivity with naturally occurring murine leukemia viruses appears to be identical to the Fv-1 locus described for sensitivity to Friend leukemia virus. Results of tissue culture studies were parallel to results of studies in vivo and indicate that the F-S virus is N-tropic and the F-B virus is NB-tropic. Inbred and partially congenic mouse strains sensitive at Fv-1 show N-type sensitivity; strains resistant at Fv-1 show B-type sensitivity. The Fv-2 locus does not appear to exert significant effect in tissue culture. Knowledge of N-B type has been useful in predicting Fv-1 sensitivity.
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PMID:A major genetic locus affecting resistance to infection with murine leukemia viruses. II. Apparent identity to a major locus described for resistance to friend murine leukemia virus. 432 33

Extracts of cultured human leukemic tissues increased the spleen focus-forming activity of Friend leukemia virus preparations in BALB/c and other partially resistant mice. Such mice carry the Fv-1(b) gene, which inhibits the expression of helper virus indigenous to the Friend virus complex, and allows co-infecting leukemia viruses of mice, cats, or chickens to substitute for the inhibited helper virus and increase the expression of the spleen focus-forming virus. The helper activity of extracts from human leukemic tissues shared several important properties with that associated with known leukemogenic viruses of animals.
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PMID:Helper activity of human leukemic tissue extracts for leukemia virus expression in mice. 433 10

Mice were infected with Friend leukemia virus and later immunized with either Vibrio cholerae vaccine or sheep erythrocytes. The primary antibody response to the bacteria (as judged by the number of plaque-forming cells) was slightly enhanced by the viral infection, whereas the response to sheep erythrocytes was inhibited. The difference appeared due to sensitization of mice to antigens crossreacting with those of sheep erythrocytes; no natural immunity to V. cholerae is detectable. However, the response of mice infected with Friend leukemia virus to a secondary challenge with the cholera bacteria was markedly inhibited. Even though the number of plaque-forming cells during the primary response was not reduced, accumulation of the cells in distinct splenic foci was suppressed. These results suggest that the effect of Friend leukemia virus on immunocompetent cells is selective. The immune response appears to be susceptible to leukemia virus-induced immunosuppression only when there has been a previous stimulation of immunocytes by antigen.
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PMID:Divergence between immunosuppression and immunocompetence during virus-induced leukemogenesis. 494 15

Infection with Friend leukemia virus causes a marked increase in the activity of splenic phosphoribosylamidotransferase in mice. Intraperitoneal injection of purine nucleotides and their free bases inhibits this enzyme. This is the first example of the control of phosphoribosylamidostransferase in vivo in the mammalian system as well as in virus-induced leukemia. Experiments in vitro support the findings in vivo.
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PMID:Phosphoribosylamidotransferase: regulation of activity in virus-induced murine leukemia by purine nucleotides. 603 94

The influence of in vivo infection with the polycythemic substrain of Friend leukemia virus on noninducible ('natural') resistance against allogeneic normal or malignant grafts was studied in lethally irradiated mice. Parallel studies were performed on the NK system in the same experimental conditions. The results indicate that FLV-P infection of mice with full (DBA/2) vs partial (BALB/c and CD2F1) susceptibility did not suppress their in vivo natural resistance against bone marrow or El-4 leukemia cells. On the other hand, a decline in NK activity paralleled the progression of leukemic disease in the more susceptible DBA/2 hosts.
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PMID:Natural resistance against hematopoietic cells in lethally-irradiated mice infected with Friend leukemia virus. 614 16

The effects of the L isomer (+)-1,2-bis(3,5-dioxopiperazine-1-yl)propane (ICRF 159; NSC 169780) on cell viability, growth, and progression through the cell cycle were investigated in suspension cultures of murine leukemia (Friend leukemia and L1210) cells and normal human lymphocytes stimulated with phytohemagglutinin and in adherent cultures derived from human neuroblastoma and Chinese hamster ovary (CHO) cells. CHO cell colony formation was inhibited by 50% following either an 8.5-hr exposure of exponentially growing cells to 10 micrograms ICRF 159 per ml or a 24-hr exposure to 3 micrograms ICRF 159 per ml. This effect was cell cycle phase specific; early G1- and G2-phase cells were more sensitive than were late-G1- or early and mid-S-phase CHO cells. Stationary-phase CHO cells were unaffected by the drug at concentrations up to 500 micrograms/ml. Incubation of L1210 cells with 3 micrograms ICRF 159 per ml for 24 hr or with 10 micrograms ICRF 159 per ml for 6 hr inhibited cell growth by 50%. In contrast, 24-hr incubation of human lymphocytes with up to 50 micrograms ICRF 159 per ml had no effect on their viability or on their ability to be stimulated by phytohemagglutinin. Constant exposure of Friend leukemia, L1210, human neuroblastoma, and phytohemagglutinin-stimulated human lymphocytes to 10.0 to 50 micrograms ICRF 159 per ml resulted in inhibition of cell division which led to cell growth at higher ploidy levels. Thus, proliferating human cells of normal or tumor origin and murine leukemic cell lines all had a similar sensitivity to the drug. Detailed analysis of cell cycle progression in L1210 cells in the presence of the drug determined that cell progression through G1 phase (G1A to G1B transition) was slowed by approximately 50%. The rate of traverse of cells through S phase was also slowed. However, the most pronounced effect was the accumulation of cells in G2 phase occurring almost immediately after addition of the drug. The data suggest that the L isomer has a range of cytotoxicity and identical cytokinetic effects similar to that of the clinically tested racemate (+/-)-ICRF 159 (NSC 129943) and, therefore, that the more soluble L isomer may have increased clinical applicability.
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PMID:Effects of the L isomer (+)-1,2-bis(3,5-dioxopiperazine-1-yl)propane on cell survival and cell cycle progression of cultured mammalian cells. 617 41

The action of 12-O-tetradecanoylphorbol-13-acetate (TPA) on several retrovirus-related functions was investigated in four virus-host cell systems. The following effects were recorded: (i) in STU-mice, infected with the Friend virus complex (Friend) murine leukaemia virus/Friend spleen focus forming virus) and treated with TPA (50 ng/g) for one week prior to infection, the number of spleen foci increased 5-fold over the control. (ii) Addition of TPA (0.04 to 40 ng/ml) to virus-producing cell systems resulted in a 2-fold increase of extracellular reverse transcriptase activity. The maximum response was observed in Friend leukemia virus-producing mouse cells at 0.1 to 0.4 ng TPA/ml and in simian sarcoma virus-producing rat cells at 4 ng/ml. (iii) The efficiency of transformation of BalbC 3T3 cells by Moloney murine sarcoma virus, tested in a focus formation assay, was slightly enhanced by TPA. (iv) TPA inhibited the induction of endogenous virus formation in B cell mitogen-stimulated spleen cell cultures from BalbC mice.
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PMID:Diverse effects: augmentation, inhibition, and non-efficacy of 12-O-tetradecanoylphorbol-13-acetate (TPA) on retrovirus genome expression in vivo and in vitro. 617 39


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