Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixty-seven specific-pathogen-free cats of various ages (newborn, 2 wk, 1 mo, 2 mo, 4 mo, and 1 yr) were inoculated ip with either the Rickard (R) or the Kawakami-Theilen (KT) strain of feline leukemia virus (FeLV). Susceptibility to FeLV was judged by induction of a) FeLV group-specific antigens (gsa) in leukocytes, b) FeLV-related disease, c) antibody to feline oncornavirus-associated cell membrane antigen (FOCMA), and d) virus-neutralizing (VN) antibody. Susceptibility to FeLV-decreased with age. Persistent viremia and FeLV-related disease developed in 100% of cats inoculated as newborns, in 85% of cats inoculated at 2 weeks to 2 months of age, and in 15% of cats inoculated at 4 months or 1 year of age. Cats susceptible to FeLV leukemogenesis became persistently FeLV gsa-positive (viremic) at 4 weeks post inoculation and thereafter and produced little or no FOCMA or VN antibody. Cats that resisted leukemogenesis by FeLV all developed persistent FOCMA and VN titers and never became FeLV gsa-positive. The disease in inoculated cats was influenced by virus strain; FeLV-R induced predominantly thymic lymphosarcoma, whereas FeLV-KT caused fatal nonregenerative anemia without concurrent neoplasia.
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PMID:Feline leukemia virus infection: age-related variation in response of cats to experimental infection. 18 71

Mutant alleles at the steel locus produce the pleiotropic effects of congenital anemia, sterility, and lack of hair pigmentation. Strain (WC/Re X C57BL/6)F1 Sl/Sld mice lived only half as long as heterozygotes and homozygous normal controls, differing only at the steel locus. Lymphocytic leukemia developed spontaneously in 37% of mice of the Sl/Sld genotype at an average age of 370 +/- 25 days and in 5% of heterozygotes and homozygous normal controls at 965 +/- 41 days. Severe ulcerative dermatitis occurred in 56% of Sl/Sld mice at an average age o4f 441 +/- 21 days and in 20% of heterozygotes and homozygous normal controls at 722 +/- 50 days. The mutant steel alleles provided an opportunity for study of the role of chronic anemia in life shortening and of a mechanism of gene action in spontaneous leukemogenesis.
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PMID:Effects of mutant steel alleles on leukemogenesis and life-span in the mouse. 31 42

Friend virus clearly provides an important model for understanding the molecular biology of cancer. Moreover, the most important aspects of the erythroleukemia can be caused by a single SFFV infection in the absence of any helper virus. The SFFV env gene encodes a membrane glycoprotein, gp55. This glycoprotein, when expressed on erythroblast surfaces, causes a constitutive mitogenesis. However, SFFV infections only rarely increase the cell's self-renewal capability or abrogate its commitment to differentiate. Therefore, the consequence of infection is initially a polyclonal erythroblastosis. This polyclonal proliferation usually leads to cell differentiation and to recovery unless helper virus is present to cause continuing infection of new erythroblasts. Extremely rare SFFV proviral integrations, however, result in abrogation of the cell's commitment to differentiate and in the concomitant acquisition of cell immortality. These immortalizing proviral integrations occur at only a small number of sites in the mouse genome. Therefore, the mitogenic and immortalizing stages of erythroleukemia are now known to be caused by discrete genetic events--the first involving the SFFV env gene and the second involving the rare proviral integration sites. In early investigations of Friend virus, the first stage always preceded the second stage by at least several weeks. Now it is known that this delay in onset of the second stage is caused solely by statistics. Every SFFV-infected erythroblast is mitogenically activated, yet only rarely does the SFFV proviral integration produce immortality. Both steps in leukemogenesis can be caused simultaneously in an erythroblast by a rare single SFFV proviral integration. There has been an explosion of interest in retroviral env gene-mediated pathogenesis. Such pathogenesis has been recently associated with most of the naturally transmitted retroviral diseases including AIDS. Such pathogenesis involves in different viruses immunosuppression, anemia, neuropathy, and leukemia (Mathes et al. 1978; Simon et al. 1984, 1987; Weiss et al. 1985; Lifson et al. 1986; Riedel et al. 1986; Sitbon et al. 1986; Sodroski et al. 1986; Mitani et al. 1987; Schmidt et al. 1987; Klase et al. 1988; Overbaugh et al. 1988a, b). The shuffling and dynamic env gene rearrangements that have been associated with murine retroviral leukemogenesis have also now been seen in FeLV-FAIDS and HIV (Fisher et al. 1988; Overbaugh et al. 1 t88b; Saag et al. 1988; Tersmette et al. 1988). Friend virus provides an important established example of such env gene pathogenesis. Although we still do not understand precisely how gp55 causes erythroblast mitosis, workers in this field have discovered important clues that may lead to answers.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Molecular biology of Friend viral erythroleukemia. 268 47

CBA/N (xid-) mice failed to develop erythroleukemia when inoculated with an NB-tropic, anemia-causing Friend virus stock (FVA), while Fv-2ss mouse strains succumbed rapidly to the characteristic Friend disease, even after a virus dose 30-fold lower than that given to CBA/N mice. Immunization with bacterial antigens or with spleen cell allografts prior to FVA inoculation rendered CBA/N mice highly susceptible to FVA. Transplantation studies confirmed that non-immunized CBA/N mice were able to both support erythroleukemic cells and permit erythroleukemic transformation, thus arguing against host defense mechanisms as a cause of resistance. On the basis of early erythroid progenitor cell sensitivity to hydroxyurea in vivo, the CBA/N strain appeared to have the FVA sensitive genotype (Fv-2ss). These results imply that CBA/N mice are not intrinsically resistant to FVA and that an as yet unknown type of immunological activity, evoked both by various immunizations and allogeneic transplantation, is required for Friend leukemogenesis in this immunodeficient inbred strain. These findings further suggest that the erythroid target cells transformed by Friend viruses are influenced by immunological activity.
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PMID:Resistance to erythroleukemia in immunodeficient xid- CBA/N mice with susceptibility after immune stimulation. 287 24

A comparative study on the expression of nuclear and cytoplasmic oncogenes was carried out using the Northern blotting technique, in Rauscher virus induced primary leukemias and the more malignant transformed cell lines derived from them. The latter grow permanently in vitro. Hyperplastic spleens obtained from mice recovering from anemia were analysed as controls. In addition to the detection of mRNAs, Southern blotting was carried out to observe whether rearrangement or amplification of oncogenes had occurred. The results show that the nuclear oncogenes c-myc, c-myb and p53 are strongly expressed in leukemic tissue, whereas c-fos transcripts show a much weaker hybridization. The expression of two of these oncogenes, c-myc and c-myb was followed during differentiation in myeloid leukemic cells and showed a gradual decrease when compared with the actin gene, which is constitutively transcribed. A large number of cytoplasmic oncogenes is expressed in the leukemic cells lines, i.e. c-abl, c-fms, c-fes, c-src, c-ros, c-H-ras, c-K-ras and N-ras. Of these, transcripts coding for c-abl and c-src were absent in blast cells of acute erythroid leukemias. Transcripts coding for c-erb, c-mos and c-sis could also not be detected. A number of putative oncogenes which are reported to play a role in Moloney and Friend virus induced leukemias for instance pim-1, fis-1, fim-1 and fim-2 were also used for screening. Only expression of pim-1 in Rauscher virus induced myeloid leukemic cells and in primary acute erythroid leukemias could be observed. At the DNA level no rearrangement or amplification of any of the oncogenes investigated could be detected. The results show that a number of oncogenes are expressed simultaneously in the same leukemic tissue or cell lines. It therefore seems likely that the presence of transcripts of different oncogenes is associated with the progression of leukemia, but is not the primary cause of leukemogenesis or of the transformation of these cells into established cell lines.
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PMID:Oncogene expression in Rauscher murine leukemia virus induced erythroid, myeloid and lymphoid cell lines. 291 75

In a large study of chromosome rearrangements occurring in human lymphocytes from normal subjects, inv (14)(q12qter) or (q11.2q32.3) is found to be the most frequent, affecting 0.15% of mitoses. The same inversion is observed in the lymphocytes of the chimpanzee, indicating the ancestry of this inversion. It is not induced by ionizing radiations, and its frequency may be increased in Fanconi anemia, but not in ataxia telangiectasia. It may represent one of the steps of the process of leukemogenesis.
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PMID:Inversion (14)(q12qter) or (q11.2q32.3): the most frequently acquired rearrangement in lymphocytes. 402 52

Leukemias induced by neonatal inoculations of several mouse strains with different strains of Friend murine leukemia helper virus (F-MuLV) were followed for time of disease onset, cytochemical analysis of predominant cell types in leukemic organs, and expression of infectious mink cell focus-inducing (MCF) viruses detected by mink cell foci or MCF-specific monoclonal antibodies. Most BALB.B and IRW mice had a rapidly appearing, severe anemia and hepatosplenomegaly consisting of erythroid cells. MCF viruses were usually isolated from enlarged spleens of IRW mice. In contrast, C57BL/10 mice had a lower incidence of disease and much slower course. Splenomegaly and lymphadenopathy with mild anemia were seen, and the predominant cell types were either myeloid (chloroleukemia) or lymphoid. MCF viruses were never isolated from this mouse strain. (C57BL/10 X IRW)F1 mice were intermediate in latency, but all mice had disease by 8 months. Myeloid, lymphoid, and some mixed leukemias with an erythroid component were observed, but in no case did we see the severe anemia or pure erythroid involvement typical of IRW and BALB.B mice. MCF viruses were, however, isolated from 22% of these mice regardless of leukemia cell type. DBA/2 mice had a disease pattern similar to the (C57BL/10 X IRW)F1 mice, and MCF viruses were isolated from three of six mice tested. Inoculation of IRW mice with the low virulence B3 strain of F-MuLV produced disease with a longer latency than F-MuLV 57, but similar cell types were transformed by both viruses. In vitro cell lines were derived from 14 mice, and most were tumorigenic in vivo. Three lines released infectious MCF virus, and three others expressed MCF-specific cell surface antigens but did not release virus. Eight lines expressed no MCF infectious virus or viral antigens. Several lines released infectious xenotropic viruses and/or expressed xenotropic MuLV cell surface antigens recognized by monoclonal antibodies reactive with xenotropic viruses. The lack of MCF expression in many primary leukemic tissues as well as in in vitro derived leukemia cell lines of C57BL/10 and (B10 X IRW)F1 mice suggested that MCF virus generation and expression may not be required for leukemogenesis in some mouse strains or in some hemopoietic lineages.
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PMID:Effect of murine host genotype on MCF virus expression, latency, and leukemia cell type of leukemias induced by Friend murine leukemia helper virus. 630 93

The effect of hematopoietic stem cell age on leukemogenesis in vitro was tested in nonrecharged, corticosterold-supplemented NIH Swiss [N:NIH(S)] mouse long-term bone marrow cultures infected with Friend murine leukemia virus of anemia-inducing strain (F-MuLV-A) or spleen focus-forming virus (SFFV) [Rauscher murine leukemia virus (R-MuLV)], a pseudotype virus derived by rescue of the SFFV genome from SFFV-Balb/3T3 clone A31 nonproducer cells with clonal helper R-MuLV. Cultures at 33 degrees C derived from 10-day-old or adult mouse marrow generated colony-forming unit culture granulocytic macrophage (CFUc) progenitor cells for over 20 weeks and colony-forming unit spleen cells for 14 weeks and generated permanent granulocytic leukemia cell lines after infection with F-MuLV-A at week 1, 2, or 4 but not at week 8. Leukemia lines were of granulocyte phenotype whether induced by F-MuLV-A or SFFV (R-MuLV) and synthesized myeloperoxidase and lysozyme but were restricted in ability to generate superoxide in response to phorbol myristate acetate stimulation. Cultures (31 degrees C) infected with temperature-sensitive (ts) helper virus mutant pseudotypes of SFFV as well as SFFV (R-MuLV) generated granulocytic leukemia lines, whereas only SFFV (R-MuLV) pseudotype virus-infected cultures became leukemic at 37 degrees C. R-MuLV wild type or ts mutant helper virus infection alone increased cell proliferation and numbers of CFUc but did not generate leukemia. These data indicated that gene(s) specific to F-MuLV-A or a virus rescued from SFFV-Balb/3T3 clone A31 nonproducer cells are required for transformation in vitro of a hematopoietic stem cell present in early but absent in late bone marrow cultures.
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PMID:Virus and cell requirements for Friend virus granulocytic leukemogenesis in long-term bone marrow cultures of NIH swiss [N:NIH(S)] mice. 692 98

The effects of the tumor-promoter phorbol myristate acetate (PMA) on normal hemopoiesis and Friend leukemia virus (FLV) granulocytic leukemogenesis in long-term bone marrow cultures were examined. FLV-anemia-inducing strain (FLV-A) infected, Rauscher R-MuLV clone M52R infected, or uninfected control NIH Swiss mouse marrow cultures were treated weekly with PMA or 4-O-methyl-PMA at 2.0 ng/ml or 200.0 ng/ml. Addition of PMA to control uninfected or R-MuLV-infected cultures decreased production of nonadherent granulocytic cells and granulocyte-macrophage progenitor cells (GM-CFU-c), and increased the numbers of adherent macrophages. Addition of PMA to FLV-A-infected cultures did not inhibit generation of granulocytic leukemia cell lines even though the numbers of adherent adipocytes were decreased and adherent macrophages were increased. PMA treatment of freshly explanted whole bone marrow but not purified nonadherent GM-progenitor cells from long-term bone marrow cultures stimulated GM-CFU-c and cluster formation in the absence of added colony-stimulating factor (CSF). The sensitivity of purified GM-progenitor cells to L929 or WEHI-3 CSF was not altered by PMA; however, PMA treatment of bone marrow macrophages or peritoneal exudate macrophages stimulated detectable GM-CFU-c and cluster formation by purified GM-progenitor cells under conditions where equal numbers of untreated macrophages failed to be stimulatory. Thus, several PMA effects on hempoietic stem cells in vitro are mediated through indirect action on adherent stromal cells including macrophages.
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PMID:Phorbol myristate acetate stimulates macrophage differentiation and replication and alters granulopoiesis and leukemogenesis in long-term bone marrow cultures. 693 21

A six-year-old girl with Fanconi anemia (FA) developed acute myeloid leukemia (AML) as the first hematologic manifestation of the syndrome. She remains in remission 18 mo after diagnosis although her management is complicated by unusual sensitivity to chemotherapeutic agents. Marrow cells studied prior to initiation of leukemia therapy showed increased chromosome breakage and an abnormal clone in which a number 7 and a number 8 chromosome were replaced by two marker chromosomes. During the present remission her cultured lymphocytes, bone marrow cells, and fibroblasts showed increased "spontaneous" chromosome breakage as well as enhanced sensitivity to the clastogenic effect of the difunctional alkylating agent diepoxybutane (DEB), features characteristic of FA. Eight months into remission 50% of her marrow cells comprised an abnormal clone, which was monosomic for the number 7 chromosome but had both copies of number 8; in addition a variable number of unique marker chromosomes were present in clonal as well as nonclonal cells. This same marrow sample, upon culture, showed an abnormal growth pattern of CFU-GM, absence of detectable CFU-GEMM and BFUe, non-responsiveness of CFU-GM to inhibition by acidic isoferritins, increased bone marrow acidic isoferritin inhibitory activity, and absence of detectable bone marrow cell-derived GM-CSF. The implications of these findings to leukemogenesis in FA are discussed.
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PMID:Acute myeloid leukemia as the first hematologic manifestation of Fanconi anemia. 695 62


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