Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After intravenous (IV) injection with factor-dependent FDC-P1 cells, irradiated DBA/2 and BALB/c mice developed transplantable leukemias owing to neoplastic transformation of the injected cells in vivo. Increasing the radiation dose shortened the preleukemic latent period, and in female mice the frequency of leukemia development was higher and the latent period shorter than in male mice. In the preleukemic period, the injected FDC-P1 cells rapidly increased in number in hematopoietic organs of irradiated animals, reaching peak levels 3 to 5 weeks after injection; factor-independent transformed cells were not detected before day 45. In unirradiated animals, these events were delayed by several weeks, and long-term survivors did not harbor detectable FDC-P1 cells. FDC-P1 cells sampled from preleukemic mice frequently showed atypical colony formation and reduced cloning efficiency in vitro, suggesting the occurrence of a distinct preleukemic change. U16.6 cells produced leukemia only in irradiated recipients, and the leukemic cells usually remained factor dependent. The two contrasting models should be of value in further analyzing the mechanisms underlying radiation-induced leukemias.
 ...
PMID:Effects of irradiation of recipient mice on the behavior and leukemogenic potential of factor-dependent hematopoietic cell lines. 240 17

DBA/2 mice engrafted with FDC-P1 cells producing high levels of the leukemia-inhibitory factor (LIF) developed high circulating levels of LIF and a fatal syndrome including the accumulation of excess osteoblasts in the marrow and new bone formation. The mice developed a neutrophil leucocytosis, an enlarged spleen, and excess numbers of hemopoietic cells in the spleen and liver. Marrow cellularity was reduced with selective survival of granulocytic cells, but the frequency of hemopoietic progenitor cells in both the marrow and spleen was higher than in control mice. Megakaryocyte numbers were reduced in marrows with pronounced sclerosis. The disease state may represent a useful model of myelosclerosis, but it remains to be established whether the hemopoietic abnormalities in these mice are direct effects of LIF or secondary changes following occlusion of the marrow by osteosclerotic tissue.
Leukemia 1989 Dec
PMID:A myelosclerotic syndrome in mice engrafted with cells producing high levels of leukemia inhibitory factor (LIF). 251 82

After cells of the non-tumorigenic-factor-dependent line FDC-PI are injected into irradiated DBA/2 mice a progressive increase occurs in the number of engrafted FDC-PI cells and eventually leukemic transformation occurs. Step-wise increase in the number of cells injected led to an increasingly rapid accumulation of untransformed FDC-PI cells in the hemopoietic organs and some shortening of the pre-leukemic phase. FDC-PI cells explanted from pre-leukemic mice differed from primary FDC-PI cells in that they were able to undergo leukemic transformation in non-irradiated recipients after short latent periods. Pre-leukemic populations contained FDC-PI variants with an improved ability to proliferate in non-irradiated tissues. Co-injection of normal marrow cells delayed the leukemic transformation of injected FDC-PI cells. The accelerating effect of prior irradiation of the recipient on leukemia development was also abrogated when the injection of FDC-PI cells was delayed by several weeks. No specific site of transformation could be determined in mice with very early leukemias. Proliferation of untransformed FDC-PI cells and the emergence of variants with improved adaptation to in vivo conditions appear to be important and possibly necessary steps in the pathogenesis of the disease. Whether the host contributes actively to the final transformation process remains speculative.
 ...
PMID:Factors influencing the time and site of leukemic transformation of factor-dependent cells after injection into irradiated recipient mice. 260 74

We previously described the interleukin 3 (IL-3)-dependent cell line, M1-A5, which has both natural cytotoxic (NC) and suppressor cell activities, the latter of which is mediated, in part, by the release of two cytokines which activate suppressor cells from unprimed lymphoid precursor cells. In this study we have compared the M1-A5 cell line with four other IL-3-dependent cell lines to determine whether these dual activities are universally associated with IL-3 dependence and to test the hypothesis that there is a direct relationship between the cytotoxic and the suppressive activities. The cell lines tested were a bone marrow derived Dexter culture derived line (FDC-P1), two Moloney leukemia virus induced leukemias (DA-1 and DA-3), and a mast cell line (PT18(A17]. All lines were dependent on IL-3 for survival but FDC-P1, DA-1, and DA-3 showed varying degrees of short-term proliferation in granulocyte-macrophage colony stimulating factor (GM-CSF). The cell lines all expressed asialo GM1 and Ly-5 surface markers but differed with respect to other markers. DA-1 expressed MAC-1, FDC-P1 and DA-3 expressed Thy-1, and PT18(A17) expressed receptors for the Fc portion of IgE. The cell lines varied greatly in their cytotoxic activity against WEHI-164. FDC-P1, DA-1, and PT18(A17) had low NC activity. DA-3 had consistently high activity, greater than that seen with M1-A5 cells. However, none of the cell lines secreted constitutively a suppressor cell inducing factor (SIF). In addition, it was demonstrated that recombinant murine TNF did not activate suppressor cells capable of inhibiting antibody synthesis and that anti-TNF did not block SIF activity, thus suggesting that TNF contamination of the M1-A5 derived SIF preparation is not responsible for the induction of suppressor cells. We conclude that suppressor cell inducing factors are not universally secreted by IL-3-dependent cell lines, that there is no correlation between NC and SIF activity, and that the dual activities of M1-A5 cells are not mediated by TNF.
 ...
PMID:Secretion of a suppressor cell inducing factor by an interleukin 3-dependent cell line with natural cytotoxic activity. III. Comparison with other interleukin 3-dependent cell lines. 297 53

An autocrine leukemia (FDC-P1-IL3) has been developed using a retroviral vector containing the interleukin-3 (IL-3) gene to transfect the IL-3-dependent cell line FDC-P1. When leukemia cells were reisolated from experimental animals, it was found that levels of interleukin-2 (IL-2) receptor (IL-2R) expression were greater on cells isolated from the lymph node than on cells isolated from the spleen. Cloned sublines of FDC-P1-IL3 were selected by flow microfluorometry for high or low levels of IL-2R expression. Those clones that expressed high levels of IL-2R grew preferentially in the lymph node. Although IL-2 is not mitogenic for FDC-P1 cells and does not increase the rate of growth of FDC-P1-IL3 cells in vitro, the cloning efficiency of FDC-P1-IL3 is increased fourfold in the presence of IL-2. These observations suggest that the IL-2R on FDC-P1-IL3 cells plays an important role in modulating the growth of this leukemia in sites that contain high levels of IL-2.
 ...
PMID:Correlation of interleukin-2 receptor expression with tissue-specific growth of an interleukin-3-dependent autocrine leukemia. 312 1

Mechanisms of leukemic cell clonal dominance may include aberrations of transmembrane signaling. In particular, neoplastic transformation has been associated with reduced capacity for hormone-stimulated adenylate cyclase activity. In the present study, prostaglandin E, a hormonal activator of adenylate cyclase that has antiproliferative activity in myeloid cells, and cholera toxin, an adenylate cyclase agonist that functions at a postreceptor site by activating the adenylate cyclase stimulatory GTP-binding protein (Gs), were studied for antiproliferative activity in two murine myeloid cell lines. FDC-P1, an interleukin 3 (IL 3)-dependent myeloid cell line and a tumorigenic IL 3-independent subline, FI, were resistant to these antiproliferative agents. The in vitro ability of the "differentiation" agent, sodium butyrate, to reverse their resistance to adenylate cyclase agonists was studied. The antiproliferative action of butyrate involved augmentation of transmembrane adenylate cyclase activity. Increased adenylate cyclase catalyst activity was the primary alteration of this transmembrane signaling group leading to the functional inhibitory effects on leukemia cells, although alterations in regulatory G-proteins appear to play a secondary role.
 ...
PMID:Restoration of adenylate cyclase responsiveness in murine myeloid leukemia permits inhibition of proliferation by hormone. Butyrate augments catalytic activity of adenylate cyclase. 312 44

Abelson murine leukemia virus (A-MuLV) has been shown to abrogate the requirement for growth factor interleukin-3 (IL-3) in a variety of hematopoietic cell lineages by a non-autocrine mechanism. By infecting an IL-3 dependent myeloid cell line, FDC-P1, with A-MuLV containing temperature sensitive tyrosine kinase mutants of the v-abl oncogene, cell lines with temperature sensitive IL-3 independence phenotype were established. At the permissive temperature, cells expressing the ts oncogenes contained 20 fold higher levels of tyrosine-phosphorylated proteins than uninfected cells and were completely IL-3 independent. When shifted to the restrictive temperature, ts A-MuLV infected cells still contained 5 to 10 fold higher levels of phosphotyrosine but became dependent on IL-3 for growth. These results demonstrate that the maintenance of A-MuLV induced IL-3 independence requires the continuous function of the v-abl oncogene.
 ...
PMID:Reversible dependence on growth factor interleukin-3 in myeloid cells expressing temperature sensitive v-abl oncogene. 325 2

Proliferation in vitro of the murine hemopoietic cell line FDC-P1 is dependent on stimulation by granulocyte-macrophage colony stimulating factor or multipotential colony stimulating factor. Although immortalized, the cells are not tumorigenic on subcutaneous inoculation. Intravenous injection of FDC-P1 cells into syngeneic DBA/2 mice was followed by the development of transplantable leukemias in 15% of nonirradiated animals and in virtually all animals that had received 100-350 rad whole-body irradiation prior to injection. Karyotypic analysis showed that the leukemias originated from FDC-P1 cells, and primary tumor cells from different animals displayed a wide spectrum of altered growth patterns when cultured in agar. In most cases, colony formation by leukemic cells in vitro exhibited autonomy with respect to stimulation by exogenous colony stimulating factors. These observations indicate that leukemic transformation of FDC-P1 cells is enhanced by irradiation of recipient mice and document a useful model for analyzing the mechanisms by which irradiation induces leukemia.
Leukemia 1988 Jun
PMID:A model system for leukemic transformation of immortalized hemopoietic cells in irradiated recipient mice. 328 20

Cells of the factor-dependent hemopoietic cell line FDC-P1 become leukemic when injected intravenously to irradiated syngeneic mice. An analysis of 117 cell lines derived from 17 such leukemic mice showed that they displayed different patterns of growth in vitro ranging from full autonomy to absolute dependency on stimulation by granulocyte-macrophage colony stimulating factor (GM-CSF) or multipotential colony stimulating factor (multi-CSF). In contrast to parental FDC-P1 cells, even the factor-dependent variant cell lines were tumorigenic in vivo. The behavior of these latter cell lines could not be explained by hyperresponsiveness to CSFs or prolonged survival in the absence of CSFs. Conditioned media and cell lysates from leukemic cell lines from 8 animals contained variable levels of GM-CSF or multi-CSF. Proliferation of a GM-CSF-producing cell line was inhibited by anti-GM-CSF antibody, while both the parental FDC-P1 line and a leukemic line secreting multi-CSF remained unaffected. The patterns of growth in vitro of the leukemic cells tended to correlate with the amounts of CSFs produced. The observations show that leukemic transformation of FDC-P1 cells in vivo is frequently linked to autogenous production of hemopoietic growth factors. The range of abnormal in vitro growth patterns observed includes those typical of human acute myeloid leukemia, and the in vivo transformation model may be useful in analyzing the mechanisms leading to the development of this human disease.
Leukemia 1988 Jun
PMID:In vitro growth patterns and autocrine production of hemopoietic colony stimulating factors: analysis of leukemic populations arising in irradiated mice from cells of an injected factor-dependent continuous cell line. 328 21

Autonomous production of a required growth factor is one mechanism by which a cell may become tumorigenic. Several leukaemias have been described which secrete growth factors which may be involved in autocrine stimulation of cell proliferation. One of these leukaemias is WEHI-3B, a myelomonocytic leukaemia that constitutively produces interleukin-3 (IL-3). Cloning of the IL-3 gene has enabled us to investigate possible genetic changes in this gene in WEHI-3B cells which may have resulted in autonomous production of growth factor. We have shown that one of the IL-3 genes in WEHI-3B has been rearranged, as a result of the insertion of a 5.1 kilobase intracisternal A-type particle genome head to head with the 5' end of the IL-3 gene, 215 bases upstream of the IL-3 TATA box. The rearranged gene, when cloned into a lambda EMBL3A vector, could readily be expressed in COS-1 monkey cells, whereas the normal gene, in the same vector, was silent. Thus the insertion of the endogenous retroviral element has resulted in abnormal expression of the IL-3 gene and is postulated to have been a key genetic change in the development of this leukaemia. In an attempt to experimentally construct IL-3 producing leukaemias, IL-3 responsive FDC-P1 and 32D cl-23 cells were transfected with a retroviral expression vector containing the IL-3 gene. This resulted in autonomous production of IL-3 and continuous proliferation of the transfected cells. As a result of transfection, the FDC-P1 and 32D cl-23 cells became leukemogenic demonstrating the oncogenic potential of abnormal expression of IL-3. The autocrine nature of the experimental leukaemias was demonstrated by blocking their proliferation with an IL-3 neutralising antiserum. Similarly treated cultures of normal bone marrow cells also produced IL-3 and could be maintained for several months after transfection but were not leukemogenic. The factor-dependent cell lines are unable to differentiate in the presence of known CSF's and presumably have undergone other genetic changes which allow them to become leukemogenic when autocrine-stimulated. In contrast, the transfected bone marrow cells could differentiate and form colonies containing mature granulocytes and macrophages. The non-tumorigenic behaviour of the transfected bone marrow cells is consistent with the concept that several other genetic changes which effectively block differentiation are required for development of tumorigenicity in these cells.
 ...
PMID:Abnormal expression of interleukin-3 and leukaemia. 331 Aug 51


<< Previous 1 2 3 4 5 6 7 Next >>