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)

Acute myelomonocytic leukemia develops in 10-30% of irradiated (300 rad) SJL/J mice, after a lag period of around one year. Additional treatment with dexamethasone shortly after irradiation increased leukemia incidence up to 50%. Experiments were conducted in order to demonstrate the existence of preleukemic cells in irradiated mice and to explore the possible role of dexamethasone, cyclophosphamide, and different hemopoietic growth factors on their promotion to overt leukemia. Transplantation of bone marrow cells from mice exposed to 300 rad plus dexamethasone into appropriate recipients, performed 4-5 months after leukemogenic treatment, resulted in acute myeloid leukemia (AML) development of donor origin in 70% of the recipients. Transfer of fractionated preleukemic bone marrow showed that the highest AML incidence developed in the recipients of fractions enriched in early hemopoietic precursors. The promoting effect of dexamethasone on preleukemic cells was confirmed by demonstrating its similar coleukemogenic effect whether administered within several hours or 130 days after radiation. Treatment with cyclophosphamide shortly after radiation could not replace the dexamethasone effect but was found to be complementary to the coleukemogenic effect of dexamethasone. Early administration of hemopoietic growth factors (starting 14 days after radiation and dexamethasone) showed that colony-stimulating factor (CSF) 1 increased the AML incidence (75%) and reduced its latency. Treatment with recombinant granulocyte-CSF (rG-CSF) had a reduced effect and recombinant granulocyte-macrophage CSF (rGM-CSF) had no promoting effect. However, administration of different factors several months after the leukemogenic treatment revealed that rGM-CSF increased AML incidence (75%) and shortened its latency, whereas rG-CSF and CSF-1 had no effect. In contrast, the late administration of recombinant interleukin 6 reduced AML incidence significantly (23%). The present results indicate that murine radiation induced AML is a multiphase process involving radiation induced preleukemia that can be promoted by different treatments.
Leukemia 1992 Jul
PMID:Initiation and promotion in radiation-induced myeloid leukemia. 162 87

Oncostatin M (OM) is a cytokine that shares a structural and functional relationship with interleukin 6, leukemia-inhibitory factor, and granulocyte colony-stimulating factor. In this report, we tested for correlations between immediate-early gene expression and some of the cellular responses elicited by OM. We determined that OM stimulated a rapid and transient elevation of EGR-1, c-jun, and c-myc mRNA in human fibroblasts prior to their proliferation. OM also stimulated a transient induction of these genes in M1 leukemic cells that differentiated into nonreplicating, macrophage-like cells. The expression of c-myc, however, decreased significantly as the cells stopped dividing. Interestingly, OM had no detectable effect on the expression of EGR-1, c-jun, and c-myc during the cell cycle arrest of human A375 melanoma cells. Our results indicate that an early nuclear event associated with OM action is the regulation of immediate-early gene expression. We suggest that the transcription factors encoded by the EGR-1, c-jun, and c-myc genes are utilized in both cell proliferation and differentiation but are not part of the mechanism by which OM inhibits A375 cell growth.
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PMID:Regulation of EGR-1, c-jun, and c-myc gene expression by oncostatin M. 163 13

Oncostatin M (OSM), a glycoprotein of Mr approximately 28,000 produced by activated monocyte and T-lymphocyte cell lines, was previously identified by its ability to inhibit the growth of cells from melanoma and other solid tumors. We have detected significant similarities in the primary amino acid sequences and predicted secondary structures of OSM, leukemia-inhibitory factor (LIF), granulocyte colony-stimulating factor (G-CSF), and interleukin 6 (IL-6). Analysis of the genes encoding these proteins revealed a shared exon organization, suggesting evolutionary descent from a common ancestral gene. Using a panel of DNAs from somatic cell hybrids, we have shown that OSM, like LIF, is located on human chromosome 22. We have also demonstrated that OSM has the ability to inhibit the proliferation of murine M1 myeloid leukemic cells and can induce their differentiation into macrophage-like cells, a function shared by LIF, G-CSF, and IL-6. We propose that OSM, LIF, G-CSF, and IL-6 are structurally related members of a cytokine family that have in common the ability to modulate differentiation of a variety of cell types.
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PMID:Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6. 171 82

After bone marrow transplantation many T-lymphocyte functions, including the production of cytokines (CK), such as interleukin 2, are severely depressed for months. The monocyte-derived cytokines tumor necrosis factor alpha and interleukin 6 are molecules central to immune functions. Moreover, they may be involved in graft-versus-host disease and in graft-versus-leukemia reaction. Hence, we have studied the reappearance of these CKs after BMT by analyzing whole blood cultures stimulated in vitro with lipopolysaccharide for 6 hr, followed by testing for the secretion of TNF in the WEHI 164/actinomycin D cytotoxicity bioassay and for IL-6 in the 7 TD 1 proliferation assay. We performed sequential studies in 6 children who were transplanted for aplastic anemia or leukemia with allogeneic bone marrow. We found that the production of both CKs can be induced as early as 10-14 days post BMT at the very beginning of engraftment, indicating that the regenerating monocyte system is recovering rapidly after BMT. Depletion and neutralization experiments confirmed that monocytes are the cellular source of the LPS-induced CK secretion after BMT. Control levels were reached 3 to 4 weeks post BMT. When analyzing the endotoxin-induced CK production in a larger panel of BMT patients after complete reconstitution, we could not detect any impact of acute or chronic GvHD, or of allogeneic or autologous BMT, nor did treatment with cyclosporine A (CsA) show any suppressive effect. Thus, our data show that the CK production of the monocyte/macrophage lineage is quite resistant to factors that do influence other cell lineages of the immune system during BMT. The coincident appearance of monocyte-derived cytokines and of GvHD suggests a role for these cytokines in GvHD in man.
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PMID:Recovery of monocytes after bone marrow transplantation--rapid reappearance of tumor necrosis factor alpha and interleukin 6 production. 192 48

Differentiation-competent clones of myeloid leukemic cells, independently isolated from the M1 cell line in Rehovot, Israel, and in Saitama, Japan, can be induced to differentiate to mature cells by the protein which we called macrophage and granulocyte differentiation-inducing protein-2 (MGI-2) that we have shown is interleukin 6 (IL-6). We now show that our MGI-2/IL-6-susceptible clones of M1 cells were not induced to differentiate with the differentiation-inducing protein called D-factor/leukemia inhibitory factor (LIF) which has also been called human interleukin for DA cells (HILDA), whereas this protein induced differentiation to macrophages in the M1 clone isolated in Saitama which was also used in Melbourne, Australia, The D-factor/LIF susceptible clone also showed a 4-fold lower sensitivity to MGI-2/IL-6 than the D-factor/LIF resistant clone. Both types of clones differentiated with interleukin-1 alpha (IL-1 alpha) and dexamethasone, whereas the D-factor/LIF resistant clone, but not the D-factor/LIF susceptible clone, was induced by bacterial lipopolysaccharide (LPS) to differentiate to mature macrophages. The present results show that clonal differences in susceptibility to differentiation-inducing proteins in the M1 cell line can explain the isolation of different differentiation-inducing proteins in M1 leukemic cells in different laboratories.
Leukemia 1989 Nov
PMID:Clonal variation in susceptibility to differentiation by different protein inducers in the myeloid leukemia cell line M1. 250 27

Different clones of myeloid leukemic cells can be induced to differentiate to mature macrophages and/or granulocytes by hematopoietic regulatory proteins and by other compounds. We now show that induction of differentiation in different clones of myeloid leukemic cells with the normal hematopoietic proteins granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), or interleukin 3 and by compounds such as dexamethasone or cytosine arabinoside (ara C) induces the expression of genes for the myeloid differentiation inducing protein MGI-2 that we have shown is interleukin 6 (IL-6) and for GM-CSF. We have previously shown that induction of differentiation with interleukin-1, IL-6, or bacterial lipopolysaccharide (LPS) also induces IL-6 and GM-CSF gene expression. Treatment of these leukemic clones with hematopoietic proteins that do not induce differentiation did not induce IL-6 or GM-CSF gene expression. The results indicate that induction of IL-6 and GM-CSF gene expression is part of the normal differentiation program in myeloid cells and support our previous evidence that there is transregulation of gene expression between different hematopoietic regulatory proteins.
Leukemia 1989 Dec
PMID:Regulation of the genes for interleukin-6 and granulocyte-macrophage colony stimulating factor by different inducers of differentiation in myeloid leukemic cells. 268 77

The effect of interleukin 10 (IL-10) on proliferation and cytokine secretion by acute myelogenous leukemia (AML) blast cells was investigated in vitro. IL-10 inhibited spontaneous AML blast proliferation for a majority of patients, whereas in the presence of exogenous growth factors (granulocyte-stimulating factor, G-CSF; granulocyte-macrophage colony-stimulating factor, GM-CSF; interleukin 3) the IL-10 effect on blast proliferation showed a wide variation depending on the individual AML patient. IL-10 seemed to cause an irreversible inhibitory effect on AML blasts, as inhibition could also be demonstrated when IL-10 was present only during the initial preincubation of the leukemia cells. IL-10 also inhibited AML blast colony formation. However, independent of the effect on AML blast proliferation, IL-10 decrease cytokine secretion from AML blast cells for all patients, as demonstrated for IL-1 alpha, IL-1 beta, tumor necrosis factor-alpha, GM-CSF and interleukin 6. IL-10 did not inhibit development of apoptosis in AML blasts cultured in vitro. Expression of complement receptors and capability to adhere and internalize bacteria by AML blasts were not altered by IL-10.
Leukemia 1995 Nov
PMID:Effects of interleukin 10 on blast cells derived from patients with acute myelogenous leukemia. 747 83

Oncostatin M (OSM) is a 28-kD glycoprotein recently identified as a growth factor for human multiple myeloma cells. It belongs to a family of distantly related cytokines that includes interleukin 6, ciliary neurotrophic factor, leukemia-inhibitory factor, and interleukin 11. These cytokines initiate signaling by inducing either homodimerization of gp130 or heterodimerization of gp130 with leukemia-inhibitory factor receptor beta components. Such dimerization in turn activates receptor-associated tyrosine kinases. In the present study using U266B1 human multiple myeloma cells, we show that OSM induces tyrosine phosphorylation and activation of JAK2, but not JAK1 or Tyk2, kinases. The results also demonstrate that OSM induces direct interaction of JAK2 kinase with Grb2, an SH2/SH3 domain containing adaptor protein. The SH2 domain of Grb2 is directly associated with tyrosine-phosphorylated JAK2. Furthermore, the presence of Sos in the JAK2-Grb2 complex suggests a role for Ras in OSM-transduced signaling.
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PMID:Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells. 750 25

The in vitro colony-forming capacities of marrow CD34-positive (CD34+) cells from 25 patients with myelodysplastic syndromes (MDS) were studied. In all patients this purified cell population showed erythroid (burst-forming unit erythroid; BFU-E) or non-erythroid colony growth, both of which were more restricted than non-purified mononuclear cell population under stimulation with erythropoietin (EPO) or granulocyte/macrophage colony-stimulating factor (GM-CSF) alone. MDS patients examined were put into two groups; refractory anemia (RA) or RA with ringed sideroblasts (RA/RARS) and RA with excess of blasts (RAEB) or RAEB in transformation (RAEB/RAEB-t). The CD34+ cells of both RA/RARS and RAEB/RAEB-t exhibited a similarity to the cells of normal individuals in their responsiveness to the addition of interleukin 6 (IL-6), IL-3 or stem cell factor (SCF). SCF caused powerful but highly variable responses in both erythroid and nonerythroid colony formation as compared with IL-6 or IL-3. We demonstrated that MDS marrow hematopoietic progenitor cells reactive to GM-CSF or EPO were additionally stimulated with early-acting hematopoietic growth factors including IL-6, IL-3 and SCF in a fashion similar to those of normal individuals.
Leukemia 1994 May
PMID:Growth analysis of marrow CD34-positive hematopoietic progenitor cells in patients with myelodysplastic syndromes. 751 49

Peripheral blood cells from a female patient with Ph1-positive chronic myelogenous leukemia (CML) in blast crisis were serially transplanted in BALB/c nude mice for 16 passages. This in vivo cell line, designated CML-N-1, had Ph1 chromosome abnormality and BCR gene rearrangement. The cells expressed CD11b, CD13, CD33, CD34, CD38, and HLA-DR antigens until the 11th passage and subcutaneous tumors produced by these passages were composed of admixtures of immature and maturing cells that differentiated to basophils when cultured in vitro. From the 12th passage on, the tumors became composed mainly of immature cells expressing CD13, CD34, and HLA-DR, and no longer differentiated to basophils even upon in vitro culture. In contrast to the vigorous proliferation in vivo, CML-N-1 cells from any passage failed to proliferate in vitro under standard liquid culture conditions with or without growth factors, such as granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, monocyte colony-stimulating factor, interleukin 3, interleukin 6 and stem cell factor. However, a continuously growing cell line, designated CML-C-1, was established by culturing CML-N-1 cells on feeder layers of mouse bone marrow stromal cells. This mouse bone marrow stromal cell-dependent cell line showed immature cell morphology and expressed early myeloid phenotype positive for CD13, CD34, and HLA-DR. These results indicate that mouse bone marrow stromal cells provide a certain growth factor(s) active on human leukemia cells.
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PMID:Direct transplantation of chronic myelogenous leukemia cells into nude mice and establishment of a leukemic stem cell (Ph1+, CD34+) line dependent on mouse bone marrow stromal cells in vitro. 754 Jun 8


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