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)

Erythroleukemia cell lines HFL/d and HFL/b, derived from tumors induced in vivo in BALB/c (H-2d) and congenic BALB.B (H-2b) mice, respectively, by a polycythemia-inducing strain of Friend virus, produced both spleen focus-forming virus (SFFV) and its native NB-tropic helper virus (Friend murine leukemia virus [FMuLV]) during early-passage generations in culture. Eventually each line ceased production of both infectious viruses but retained its tumorigenic potential in syngeneic hosts. Virus-producer and -nonproducer clones of these cell lines were examined for expression of proteins encoded by the SFFV or FMuLV genomes. Lysates of labeled cells were treated with various antiviral sera, and the precipitates were examined by gel electrophoresis. Expression of the FMuLV env gene-encoded precursor protein, gPr84env, was observed in all producer and most nonproducer clones, but the FMuLV gag and pol gene products, Pr65gag and Pr200gag-pol, were uniformly undetectable in nonproducer clones. All HFL/d and HFL/b clones expressed appreciable amounts of the SFFV-encoded envelope protein, gp52, including one exceptional clone which had ceased to express any FMuLV-encoded proteins. The molecular weight of this SFFV-encoded envelope protein was consistently smaller in all HFL/b clones than in HFL/d clones, regardless of their producer or nonproducer status. The virus-nonproducer phenotype thus appears to be due to shutdown of expression of the 5' portion of the FMuLV genome in two independent cell lines.
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PMID:Viral protein expression in producer and nonproducer clones of friend erythroleukemia cell lines. 693 35

Tumor formation by subcutaneous transplants of spleens from erythroleukemic mice infected with Friend virus complex inducing polycythemia (FLV-P) is successful only during the late phase of the disease. To determine whether this observation is due to the absence of tumorigenic cells in the early phase of such leukemia or to the inability of standard procedures to detect these cells, the sensitivities of different routes of inoculation in sublethally irradiated or unirradiated syngeneic recipients were examined. The omentum of the sublethally irradiated mouse was found to be a suitable site for the homing and proliferation of recently isolated tumorigenic cells from FLV-P-infected mice, since it proved 1,000 times more sensitive than the usual subcutaneous sites in unirradiated mice. When this sensitive graft in the omentum was applied to detection of tumorigenic cells in the spleens of FLV-P-infected mice, the mean detection time was 20 days after virus infection, compared to 36 days with the usual subcutaneous graft method.
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PMID:Detection of tumorigenic cells in Friend virus-infected mice: an in vivo methodological investigation. 694 Oct 43

In long-term marrow cultures, hemopoiesis can be maintained for several months, although erythropoiesis is normally suppressed at the most primitive level of development (the erythroid colony-forming cells). Infection of these cultures with a viral complex combining helper-independent murine leukemia virus (F-MuLV) and a spleen focus-forming virus (SFFVp) results in a productive infection of both the replication defective SFFVp and the F-MuLV. After infection, the cultures show a dramatic elevation in the numbers of late erythroid progenitor cells (CFU-E), many of which will grow in the absence of added erythropoietin, and a transient erythropoietin, independent erythropoiesis, including the production of mature, enucleated erythrocytes. Hemopoiesis eventually declines, with no evidence for the generation of Friend tumor cells. When erythropoiesis is induced in the long-term cultures by addition of anemic mouse serum before infection by polycythemia-inducing Friend virus, the generation of erythropoietin-independent CFU-E and erythrocyte formation is followed by the sustained production (greater than 40 wk) of primitive erythroid cells with low spontaneous levels (less than 5%) of hemoglobinization. Although these cells will produce spleen colonies in irradiated mice and can be cloned in soft-gel media, they do not produce autonomous, permanently growing cell lines in vitro, i.e., they retain a dependency upon the marrow-adherent layer for their continued growth. However, following a further passage on a "virgin" marrow environment, permanent cell lines can be established that are able to grow independently of environmental influences. Thus, this system is the first description of a complete in vitro system for the reproducible production and isolation of Friend virus-induced erythroid cell lines.
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PMID:Friend disease in vitro. 694 38

The paper presents an evaluation of 1.236 cases of different forms of leukemia. Malignant tumors of different localizations were identified in 21 cases (1.7%). Neoplasms were most frequently associated with chronic lymphoid leukemia (4%), followed by osteomyelosclerosis (1.3%), chronic myeloleukemia (1%), polycythemia (0.9%) and acute leukemia (0.44%). A case of chronic myeloleukemia with concomitant myelosarcoma, thyroid cancer, malignant tumor of kidney and cortical adenoma is presented. The role of immunological disorders and cytostatic therapy in the genesis of "secondary" tumor are discussed.
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PMID:[Malignant neoplasms in leukemias]. 694 37

The specificity of murine leukemia virus-induced myelomonocytic phenotypic changes in long-term bone marrow culture have been examined by comparing the effects of polycythemia-inducing Friend leukemia virus (FVP) and Moloney murine leukemia virus (M-MuLV) known to have in vivo target cells in the erythroid and lymphoid lineage, respectively. Noninfected adn M-MuLV-infected cultures showed no modification in granulocyte macrophage colony-forming cell behavior and failed to generate cell line in WEHI-3-conditioned medium. In contrast, in FVP-infected cultures, granulocyte macrophage colony-forming cells became colony-stimulating factor independent, and the nonadherent cells gave rise to two cell lines in WEHI-3 conditioned medium with monocytic characteristics and no leukemogenic potential in vivo. These results confirm the ability of long-term bone marrow culture to unmask target cells for FVP within myelomonocytic progenitors, and the negative results in M-MuLV-infected cultures underline the specificity of the FVP-induced phenotypic changes. Despite a high level of virus production and the presence of T-cell precursors in the M-MuLV infected culture, T-cell transformation was not observed.
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PMID:Comparative effects of polycythemia-inducing Friend leukemia virus and Moloney leukemia virus on hematopoietic progenitors in murine long-term bone marrow cultures. 697 4

Uninfected DBA/2 mice and those infected 12 days previously with the polycythemia-inducing Friend murine leukemia virus were treated with 5-FU in doses of 18.75--200 mg/kg ip, and the effects on spleen weight, reticulocytosis, and hematopoietic stem cell compartments CFU-S, CFU-C, and CFU-E was studied. The CFU-E population of virus-infected mice, which had been completely independent of erythropoietin (Ep) in vitro before treatment, showed a considerable proportion of normal Ep-requiring CFU-E at Days 2--6 after doses less than or equal to 50 mg/kg, indicating a chemotherapy-induced remission. Later, Ep-independent growth was seen again, most probably due to a reinfection by the virus at the target cell level. The regeneration of all stem cell types was quicker in uninfected mice than in those infected with virus. These data are discussed in relation to results obtained with hydroxyurea treatment, where Ep-dependent CFU-E were also seen, and with respect to the effects of busulfan, carmustine, and dactinomycin, with their different modes of actin. The importance of effective antiviral therapy for the cure of such a virus-induced malignancy is emphasized.
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PMID:Hematopoietic stem cells in Friend murine leukemia virus-infected mice undergoing chemotherapy: effects of 5-FU. 713 39

Friend spleen focus-forming virus (F-SFFV) causes acute erythroleukemia in mice and encodes in its defective env gene an Env-like membrane glycoprotein (gp55). The F-SFFV env gene has three characteristic structures compared with that of ecotropic murine leukemia viruses (MuLVs): substitution by the polytropic MuLV env sequence, a 585-bp deletion, and a 1-bp insertion. All of these characteristic structures are essential for the leukemogenic potential of gp55 of polycythemia-inducing isolates of F-SFFV (F-SFFVp). The 1-bp insertion causes changes of six amino acids and truncation by 34 amino acids at the C terminus. In this study, we constructed 12 mutant F-SFFV genomes starting from the wild-type F-SFFVp and examined the effect of the C-terminal truncation and the six altered amino acids on the pathogenic activity of gp55. The results indicated that at least 18 to 24 amino acids must be deleted from the C terminus for the env product to be pathogenically active. We also found that the six altered amino acids contributed significantly to the pathogenic activity of gp55. Analyses of the cellular processing of these mutant gp55s supported a correlation between the pathogenic activity of gp55 and its efficiency in overall cellular processing.
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PMID:Both the changes of six amino acids and the C-terminal truncation caused by a one-base insertion in the defective env gene of Friend spleen focus-forming virus significantly affect the pathogenic activity of the encoded leukemogenic membrane glycoprotein (gp55). 749 68

Synthetic peptide vaccines containing a single Th cell epitope identified in the gp70 envelope glycoprotein of Friend murine leukemia helper virus induced potent protective immunity against Friend virus infection. H-2a/b mice immunized by a single s.c. injection of the CFA emulsion containing a peptide that represented the N-terminal gp70 epitope recovered slowly from initial development of splenomegaly, and most did not develop late leukemia, whereas most of the control mice given an injection of CFA alone showed sustained leukemic splenomegaly after the challenge with Friend virus. The mice of the same genetic background immunized with the C-terminal Th cell epitope by a single injection of a separate synthetic peptide eliminated virus-producing cells from the spleen within 12 days after inoculation of Friend virus complex, and did not develop early splenomegaly or polycythemia. H-2a/a mice were not protected by immunization with either one of the two synthetic peptides. Earlier production and more rapid class switching of virus-neutralizing Abs were observed in H-2a/b mice immunized with the peptide vaccines after the challenge with Friend virus, compared with the responses of the control mice. Detailed kinetic and immunohistopathologic analyses suggested that Th cells might be directly involved in the growth inhibition and elimination of virus-infected erythroid precursor cells.
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PMID:Immunization with a single T helper cell epitope abrogates Friend virus-induced early erythroid proliferation and prevents late leukemia development. 754 23

D-aspartic beta-hydroxamate (DAH), an aspartic acid analog, exerts antitumoral activity on murine leukemia L5178Y, both in vitro and in vivo. In this study, we show that DAH is also active in vivo against Friend virus (FV-P)-induced erythroleukemia, and we report the effects of DAH in vivo an in vitro on FV-P target cells, i.e. the mature erythroid colony-forming cells (CFU-E). DAH treatment (2 g/kg/day) given for 95 days as a single daily i.p. injection to DBA/2 mice either 3 or 12 days following inoculation with a high dose (10(3) plaque-forming units) of FV-P resulted in a marked increase in the mean survival time of treated animals (212 and 191%, respectively). Since FV-P elicits spleen enlargement and polycythemia, we examined the effects of DAH on spleen size, spleen-nucleated cell number, and hematocrit, in normal and FV-P infected mice, at different times in the course of continuous DAH treatments. DAH treatment initiated 3 days after viral infection inhibits the virus-induced splenomegaly, with at day 26 p.i. 1.15 x 10(8) and 12.6 x 10(8) nucleated cells per spleen observed in DAH-treated mice and untreated mice respectively, whereas only 1.03 x 10(8) nucleated cells were observed in uninfected mice. Furthermore, DAH prevents virus-induced polycythemia: on day 26, an hematocrit of 39% was measured in DAH-treated mice as compared to 60% in untreated mice. DAH treatment initiated 12 days after viral infection reduces splenomegaly, the number of nucleated spleen cells and the hematocrit of infected mice. DAH treatment initiated 3 days after viral infection prevents the tremendous increase of CFU-E in the spleen of infected mice: on day 11, the spleen of infected mice contained 4.6 x 10(6) CFU-E, while the spleen of treated mice only contained 26 x 10(3) CFU-E, and on day 26 the spleen CFU-E numbers were 45.4 x 10(6) and 1.5 x 10(6) in untreated and treated infected mice, respectively. In control uninfected mice, DAH treatment induced a transient decrease in spleen CFU-E followed by a rebound phenomenon. In vitro, preincubation with DAH inhibits colony formation by FV-P infected CFU-E, at doses starting at 3 mM, as compared to uninfected CFU-E. These data show that DAH inhibits the expression of the retroviral infection, and appears to preferentially inhibit the proliferation of infected target cells (CFU-E) in vivo.
Leukemia 1994 Oct
PMID:Antiproliferative effect of D-aspartic acid beta-hydroxamate (DAH) on Friend virus-infected erythropoietic progenitor cells. 793 66

D-aspartic acid beta-hydroxamate (DAH), an aspartic acid analogue, exerts anti-tumoral activity against murine leukemia L5178Y both in vitro and in vivo. We show here that DAH displays activity against Friend leukemia cells (FLC) in vitro: a concentration of 2 mM results in a total inhibition of cell growth. DAH is also active in vivo against Friend virus (FV-P)-induced erythroleukemia. Treatment with DAH, given for 95 days as a single daily i.p. injection to DBA/2 mice 3 days following FV-P inoculation, induced a marked increase of 212% in the mean survival time (MST) of treated animals. Since FV-P-induced erythroleukemia is characterized by the proliferation of mature erythroid precursors, we examined the effect of DAH treatment on erythroid colony-forming cells (CFU-E) and observed that the number of CFU-E per spleen was 30 times lower in DAH-treated mice than in the controls. To gain further insight into the early effects of DAH treatment on the early phase of Friend disease, we examined the effects of short DAH treatment on spleen size, hematocrit and viremia in FV-P-infected mice. DAH treatment initiated 3 days post infection (p.i.) inhibited splenomegaly, prevented virus-induced polycythemia, and reduced serum viremia. Late DAH treatment (18 days p.i.) induced regression of FVP-induced disease as evidenced by reduction of spleen weight.
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PMID:Therapeutic effects of D-aspartic acid beta-hydroxamate (DAH) on Friend erythroleukemia. 805 Aug 23


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