Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598766 (leukemogenesis)
 4,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of Rauscher virus-induced erythroleukemia have demonstrated immunodepressive effects in the host and enhanced leukemogenesis with adjuvant administration. These observations led to the study of leukemic development in the NZB strain as a natural model of the experimentally adjuvant-stimulated animal. The results of such investigation would attribute the increased susceptibility of NZB mice to the possession of an enlarged population of pluripotent hemopoietic stem cells in active cell cycle. Studies with radiation chimeras have further shown that elevated endogenous spleen colony formation, the increased potential for autoimmunity, and for susceptibility to Rauscher viral leukemogenesis are all linked through the NZB hemopoietic system. It is concluded that the presence of an enlarged compartment of cyclically active stem cells may be an etiologic factor in the susceptibility to both virus-induced leukemia and the development of autoimmune disease.
 ...
PMID:Tumor virus effects on immunocyte precursor cells. Hemopoietic stem cell behavior and leukemogenic susceptibility. 108 86

AKR mice spontaneously develop T-cell leukemias in the thymus late in the first year of life. These neoplasms arise following the appearance in the thymus of a recombinant retrovirus but can be prevented by thymectomy, indicating a role for both virus and elements of the thymic microenvironment in leukemogenesis. The intrathymic appearance of recombinant retrovirus was examined at ages leading up to leukemogenesis in order to identify and characterize the microenvironments in which the virus is first expressed. A stromal cell, the macrophage, was found to be the first thymic element to produce detectable levels of recombinant retrovirus, approximately 12 weeks before thymocytes. This observation provides a mechanism to reconcile viral leukemogenesis with the requirement for an intact thymus. Thus, a nonlymphoid cell, the macrophage, may play a critical role in the development of lymphoid neoplasia.
 ...
PMID:Macrophages are the first thymic cells to express polytropic retrovirus in AKR mouse leukemogenesis. 192 Jun 31

Proliferation in total populations of thymocytes from control AKR mice or AKR mice injected intrathymically with MCF 69L1 virus was measured by flow cytometry of acridine orange-stained cells. Cell sorting experiments showed that the majority subpopulations of small cortical and medullary thymocytes in control mice were noncycling and were predominantly in the Go phase of the cell cycle. Of the 15 to 20% cycling thymic lymphoblasts, approximately 50% were in the G1 phase, 35% were in the S phase, and 15% were in the G2 + M phases of the cell cycle. Cycling cells appeared to consist of a major subpopulation with low RNA content and a minority subpopulation with high RNA content. In virus-injected mice, no changes in cell cycling were observed at stage I of leukemogenesis (30 to 40 days postinjection), at which time infection of thymocytes by MCF virus is maximum and constant but no clonality is evident. Thus, MCF virus infection of thymocytes per se does not appear to alter cell proliferation. Increased cell cycling and a shift in cell cycle distribution to more cells in G1 was observed at stage II of leukemogenesis (50 to 60 days postinjection), at which time a clonally expanded cell population is known to emerge in thymuses of injected mice. Acridine orange staining resolved these novel cycling cells from subpopulations of normal thymic lymphoblasts on the basis of intermediate RNA content. The transition from stage II to stage III (50 to 60 days postinjection) was accompanied by the outgrowth of a major cycling population with a distinct, often increased, RNA content. As a result, the residual "normal" background of cycling cells often observed in stage II was markedly reduced or completely absent by stage III. Populations of cycling blasts from mice with frank leukemia differed from those at stage III by a variability in mean RNA content and in cell cycle distribution indicative of individual tumor heterogeneity. In addition, thymomas often contained multiple populations of cycling blasts that could be resolved by their discrete RNA distributions. Simultaneous staining of DNA and RNA by acridine orange appears particularly well-suited for studying a heterogeneous population of cycling and noncycling cells represented by mouse thymus. This method has permitted a rapid and quantitative analysis of cell cycle parameters at progressive stages of viral leukemogenesis in AKR mice.
 ...
PMID:Changes in thymocyte proliferation at different stages of viral leukemogenesis in AKR mice. 241 23

Blot hybridization of thymocyte DNA from AKR/J mice was used to detect new proviral junction fragments as markers of clonality at different stages of viral leukemogenesis and to detect DNA rearrangements at the c-myc locus due to proviral insertion. Clonal populations of thymocytes were observed in mink cell focus-forming virus-injected mice as early as 35 days postinjection, at a stage distinguishable from frank leukemia by flow cytometric analysis and transplantation bioassay. Specific proviral integrations in the c-myc locus were detected in 15% of these early clones and in up to 65% of late-developing thymomas and frank leukemias. Thus, in this system c-myc activation appears to be a common mechanism in T-cell leukemogenesis.
 ...
PMID:Early clonality and high-frequency proviral integration into the c-myc locus in AKR leukemias. 299 74

Henry Kaplan helped establish the fields of lymphocyte biology and viral leukemogenesis by his early and continuing studies on radiation leukemogenesis. As one of Henry's students I carried on these dual preoccupations with thymic lymphocytopoiesis and thymic lymphomagenesis. This communication demonstrates that thymic lymphocytes are derived from bone marrow precursors which lack any T cell markers; these bone marrow cells (or their clonogenic subsets) can give rise to either thymic cortical plus medullary progeny, or medullary progeny alone; thymic lymphocytes mature in contact with 3-5 classes of nonlymphoid cells (thymic nurse cells, cortical dendritic epithelial cells, medullary epithelial cells, dendritic reticular cells, and macrophages), and one of these subsets, cortical dendritic epithelial cells, express an unusual distribution of MHC antigen (perhaps utilized in the maturation of T cell MHC restriction); the population of cells which are poised to emigrate from the thymus are a unique subset of cortical cells which possess peripheral lymphoid organ homing receptors; and the thymic target cells for retrovirus lymphomagenesis express highly specific retrovirus receptors that are analogous (and perhaps synonymous) with antigen-specific T cell receptors.
 ...
PMID:Thymic lymphocyte differentiation and thymic leukemogenesis. 387 34

Previous studies have demonstrated that spleen cells from DBA/2 mice protected against challenge with a leukemogenic dose of Friend leukemia virus (FLV) by passive administration of xenogeneic antiviral or anti-FLV Mr 71,000 viral envelope glycoprotein antisera can adoptively transfer antiviral resistance to unimmunized irradiated syngeneic recipients. In addition, elimination of T-cells by treatment with anti-Thy 1.2 antibodies plus complement had no effect on the ability of spleen cells from serum-protected mice to adoptively transfer antiviral resistance. We now show that similar depletion of B-cells with rabbit anti-mouse immunoglobulin G plus complement or macrophages by adherence to Sephadex G-10 columns also leaves intact the protective capacity of spleen cells from serum-protected mice. That these results reflect the ability of more than one spleen cell population to transfer antiviral resistance rather than the activity of a non-T, non-B, nonmacrophage cell compartment is supported by the finding that purified splenic T- or B-cells alone from serum-protected DBA/2 mice can adoptively transfer antiviral resistance. Given the previously reported effects of sublethal irradiation on FLV leukemogenesis which could potentially complicate the interpretation of adoptive transfer experiments carried out in this system, analogous studies were performed using a Winn-type assay in which putative effector cells were preincubated with virus before inoculation of the mixture in unirradiated mice. These Winn assay experiments yielded identical results in that serum-protected spleen cells again prevented viral leukemogenesis, and the separate elimination of T-cells, B-cells, or macrophages had no effect on their protective activity. In addition, mixed transfer of serum-protected and normal spleen cells also protected irradiated mice against FLV challenge, providing further evidence that this adoptive protection truly reflects the presence of virus-specific effector cells in the spleens of serum-protected mice and not an inability of these spleen cells to replace radiation-sensitive viral target cells in recipient animals, since these should be supplied by the normal spleen cells in the transferred mixture.
 ...
PMID:Use of adoptive transfer and Winn assay procedures in the further analysis of antiviral acquired immunity in mice protected against Friend leukemia virus-induced disease by passive serum therapy. 660 7

Friend spleen focus-forming virus (F-SFFV) is a replication-defective acutely leukemogenic mouse retrovirus and encodes an envelope protein (Env)-like membrane glycoprotein (gp55) in its defective env gene, which is responsible for the early stage of the viral leukemogenesis. Gp55 is a modified Env protein and contains a polytropic mink cell focus-inducing (MCF) murine leukemia virus (MuLV) Env gp70-derived sequence in its amino-terminal region. To evaluate the possibility that the presumed binding of gp55 to an MCF MuLV receptor protein has some role in leukemogenesis, we examined the biological activities of a mutant gp55 (XE gp55), which has a xenotropic MuLV Env gp70 amino-terminal region. XE gp55 displayed almost the same biological activities as the wild-type gp55, excluding the above possibility.
 ...
PMID:Pathogenicity of a mutant friend spleen focus-forming virus encoding an Env-like membrane glycoprotein (gp55) with substitution by a xenotropic murine leukemia virus Env gp70 sequence. 962 23

Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4(+) T cells caused by the human T-cell leukemia virus type 1 (HTLV-1). The viral leukemogenesis is critically dependent on its oncoprotein Tax because the protein as well as the virus can immortalize primary human lymphocytes to permanent growth. As a transcriptional transactivator, Tax can stimulate the expression of distinct cellular genes. Alterations in the expression levels of unknown growth-relevant genes may contribute to the changed growth properties of Tax-immortalized and leukemic cells. To identify genes that are linked to Tax transformation and ATL leukemogenesis, this study systematically compared the gene expression of cultured cells from patients with acute ATL with that of stimulated peripheral blood T lymphocytes. Several overexpressed RNAs that encode signal transduction functions were identified. These include a dual-specific protein phosphatase (PAC1), an interferon-inducible factor (ISG15), a basic helix-loop-helix transcription factor (DEC-1), and the secreted antiapoptotic chemokine I-309. The ATL cell culture supernatants contained an antiapoptotic activity that could be specifically inhibited by antibodies directed against I-309. Inhibition of I-309 receptor (CCR8) signaling by pertussis toxin increased the apoptosis rate of ATL cell cultures in the presence and absence of external apoptotic stimuli. Both the I-309--specific antiapoptotic activity and the proapoptotic effect of inhibitors of I-309 signaling suggest the existence of an antiapoptotic autocrine loop in ATL cells. Thus, the overexpression of this chemokine may inhibit apoptosis in ATL cells and could substantially contribute to their growth. (Blood. 2001;98:1150-1159)
 ...
PMID:Autocrine antiapoptotic stimulation of cultured adult T-cell leukemia cells by overexpression of the chemokine I-309. 1149 64