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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Gene-therapy of blood-borne disorders may be best achieved using hematopoietic stem cells (HSC) which have extensive self renewal potential as well as multilineage repopulating potential as a cellular target. The human HSC, which is CD34+Thy-1+Lin- has been isolated from fetal, adult bone marrow and cytokine-mobilized peripheral blood (MPB) (1-3). Results presented in this study show that the degree of mobilization of HSC into peripheral blood of cancer patients is highly variable and that the combined use of high dose chemotherapy and GM-CSF as a mobilization strategy is superior to the use of G-CSF with regard to the mobilization of true HSC. A multistep cell isolation procedure has been developed which utilizes high speed flow-cytometric cell sorting and allows the isolation of sufficient numbers of HSC from MPB to permit their use as an hematopoietic graft for clinical transplantation. Hematopoietic stem cells isolated from MPB are capable of self-renewal and differentiation into multiple hematopoietic lineages as shown by their behavior in both in vitro and in vivo assays. Mobilized PB mononuclear cells isolated from cancer patients are frequently contaminated with tumor cells. Using this cell isolation procedure, HSC preparations from patients with multiple myeloma have been created with greatly reduced tumor cell burdens. These CD34+Thy-1+Lin- cells are capable of being stably transduced at high efficiency (32-75%) by co-culture on a cell line producing recombinant retroviruses containing the neomycin-resistant gene. These HSC cell populations are likely ideal targets for hematopoietic cell-based gene therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Leukemia 1995 Oct
PMID:Cytokine-mobilized peripheral blood CD34+Thy-1+Lin- human hematopoietic stem cells as target cells for transplantation-based gene therapy. 747 7

A novel hematopoietic growth factor for primitive hematopoietic progenitor cells, the ligand for the flt3/flk2 receptor, (FL), has been recently purified and its gene has been cloned. In the present study, we investigated the effects of FL on the proliferation and differentiation of normal and leukemic myeloid progenitor cells. We demonstrate that FL is a potent stimulator of the in vitro growth of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), or G-CSF-dependent granulocyte-macrophage committed precursors from Lin- CD34+ bone marrow cells of normal donors. By contrast, FL does not affect the growth of erythroid-committed progenitors even in the presence of erythropoietin. The effect of FL on the proliferation and on the in vitro growth of clonogenic leukemic precursor cells was studied in 54 acute myeloid leukemia (AML) cases. Fresh leukemia blasts from 36 of 45 patients with AML significantly responded to FL without any relation to the French-American-British (FAB) subtype. FL stimulated the proliferation of leukemic blasts in a dose-dependent fashion. Synergistic activities were seen when FL was combined with G-CSF, GM-CSF, IL-3, or stem cell factor (SCF). FL as a single factor induced or increased significantly colony formation by clonogenic precursor cells from 21 of 24 patients with AML. In the presence of suboptimal and optimal concentrations of G-CSF, GM-CSF, IL3, SCF, or a combination of all factors, FL strongly enhanced the number of leukemic colonies (up to 18-fold). We also evaluated the induction of tyrosine phosphorylated protein on FL stimulation in fresh AML cells. We demonstrate that, on FL stimulation, a band of phosphorylated protein(s) of about 90 kD can be detected in FL-responsive, but not in FL-unresponsive cases. This study suggests that FL may be an important factor for the growth of myeloid leukemia cells, either as a direct stimulus or as a synergistic factor with other cytokines.
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PMID:Effects of human FLT3 ligand on myeloid leukemia cell growth: heterogeneity in response and synergy with other hematopoietic growth factors. 749 67

Somatostatin (SS) is a 14 amino acid peptide which is secreted by the hypothalamus and the pancreatic islets. It expresses antiproliferative activity in various organ systems, experiments have suggested effects of SS on hematopoietic cells. Here we present investigations regarding the effect of SS and its analog SMS 201-995 (SMS) on the in vitro proliferation of acute lymphoblastic leukemia (ALL; n = 7 cases), acute myeloid leukemia (AML; n = 21 cases) and chronic lymphocytic leukemia (CLL; n = 2 cases). Both SS and SMS inhibited spontaneous leukemic cell growth in approximately 1/3 of cases (i.e. 7/19). G-CSF stimulated AML cells were inhibited by SMS in 11/21 cases. AML cell proliferation induced by IL-3 or GM-CSF was suppressed in only 3/21 and 6/21 cases, respectively. In ALL cells, IL-7-induced proliferation was suppressed by SMS in 3/7 cases. The effect of SMS seemed to depend on the type of the hematopoietic growth factor, and on their concentrations. In fact, high concentrations of G-CSF could override SMS blocking completely. Colony formation by normal marrow progenitors and DNA synthesis by HL-60 and T11/65 leukemic cell lines were not affected by SMS. In conclusion, somatostatin may act as a negative regulator of the proliferative activity of human leukemia.
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PMID:Somatostatin and its cyclic octapeptide analog SMS 201-995 as inhibitors of proliferation of human acute lymphoblastic and acute myeloid leukemia. 750 Jun 46

The trans-activator protein, tax, from the human T leukemia virus type 1 (HTLV-1) trans-activates both viral and cellular genes. It has previously been shown that granulocyte macrophage-colony stimulating factor (GM-CSF) is constitutively expressed in HTLV-1 infected cells and in cells artificially expressing tax. We show here that the GM-CSF promoter is tax responsive in fibroblasts and T cells, whereas the granulocyte (G)-CSF promoter is tax responsive only in fibroblasts. The tax protein can activate cellular genes through a least two families of transcription factors; the NF-kB/rel and CREB/ATF families. We have used mutant tax proteins to show that the activation of NF-kB proteins is essential for tax trans-activation of both the GM-CSF and G-CSF promoters. The ability of tax to activate CREB/ATF proteins is also essential for GM-CSF transactivation. We have identified a 44 bp region of the GM-CSF promoter that contains tax responsive elements. This region contains a classical NF-kB site, a CK-1 element that can bind the NF-kB p65 protein, as well as a putative ATF binding site. The tax response of the G-CSF promoter requires not only the conserved CK-1 sequence but also an adjacent NF-IL6 binding site that may explain the cell restricted function of the G-CSF promoter.
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PMID:HTLV-1 tax activation of the GM-CSF and G-CSF promoters requires the interaction of NF-kB with other transcription factor families. 750 30

Granulocyte--colony stimulating factor (G-CSF, filgrastim) is a glycoprotein hormone of the hematopoietin family that primarily influences the proliferation and differentiation of neutrophilic granulocytic precursors. As with all glyco-protein hormones, G-CSF interacts with target cells by binding to specific cell-surface receptors. It stimulates proliferation, differentiation and activation of cells of the neutrophil--granulocyte lineage and has been investigated as therapy for patients with various neutropenic conditions. A major use for recombinant G-CSF therapy will be in ameliorating the neutropenia which follows cytoreductive chemotherapy. The increase in neutrophils produced by this factor render it a useful treatment for conditions such as congenital, acquired and cyclic neutropenias. It may be an effective therapy in myelodysplasia and aplastic anaemia. G-CSF is also useful in accelerating the recovery of transplanted bone marrow in patients with leukaemia, lymphoma and solid tumors. G-CSF is well tolerated. The most frequently reported adverse effect is mild to moderate bone pain.
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PMID:[Biological properties and clinical application of filgrastim (G-CSF)]. 750 84

Acute myelogenous leukemia is characterized by the infinite proliferation of malignant leukemia cells and by the impaired hematopoiesis. The proliferation of leukemia cells is supported by a small subpopulation, leukemic blast progenitors. Leukemic blast progenitors make leukemic blast colonies in methylcellulose culture. To determine the mechanism by which leukemia cells proliferate, we studied the role of several cytokines in the proliferation of leukemic blast progenitors in vitro. The findings indicated that there are at least three types in the regulation by cytokines of the leukemic cell growth. One is the stimulation of leukemic blast progenitors by colony-stimulating factors(CSFs) or interleukins(ILs) added in culture. These cytokines include granulocyte-CSF(G-CSF), granulocyte-macrophage CSF (GM-CSF), IL-3 and IL-1. The second is the autocrine growth mechanism. Leukemia cells by themselves produce and secrete G-CSF and GM-CSF, which stimulate the growth of leukemic blast progenitors. The third is a complex mechanism. IL-1, produced by leukemia cells or other cells, enhances the production of GM-CSF by leukemia cells, which stimulates the growth of leukemic blast progenitors. The precise mechanism by which each cytokine acts on leukemic blast progenitors should be determined to explore the mechanism of leukemia cell growth.
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PMID:[The role of cytokines in the proliferation of leukemia cells in acute myelogenous leukemia]. 750 32

In human long-term marrow cultures granulomonopoiesis is maintained for several weeks. Studies on granulomonocytic progenitors (CFU-GM) and their progeny have shown that survival, proliferation, differentiation and maturation of these cells are controlled by a set of glycoproteins, the colony-stimulating factors (CSFs) and the Steel factor. We have studied the expression of these factors using reverse transcriptase polymerase chain reaction (RT-PCR) in 17 adherent layers of normal bone marrow at 3, 5 or 7 weeks of culture. We have taken the 5637 bladder carcinoma cell line as a control for expression of GM-CSF, M-CSF, G-CSF and Steel factor, and PHA-activated T lymphocytes as a control for expression of multi-CSF (interleukin 3, IL-3). We have found that GM-CSF was expressed in the 17 adherent layers without induction by interleukin 1 beta (IL-1 beta). M-CSF was also detected in all cases, but in two early-stage (week 3 and week 5) cultures only after stimulation by IL-1 beta. G-CSF was detected in only 11 cases (three without IL-1 beta, and eight after addition of IL-1 beta). Steel factor was detected in 14 cases (ten without IL-1 beta, and four after addition of IL-1 beta). IL-3 was not detected even by means of nested RT-PCR. These data indicate in six late-stage (week 5 or week 7) cultures G-CSF messenger concentrations 10(3)-fold less than in 5637 control cells (for an identical amount of total cellular RNA). A similar conclusion may be drawn for Steel factor in three late-stage cultures. For IL-3 our negative results indicate a messenger concentration 10(5)-fold less than in activated T lymphocytes. These results suggest a crucial role for GM-CSF and M-CSF in the maintenance of granulomonopoiesis in human long-term cultures. The role of G-CSF and Steel factor may be more marginal. Eventually IL-2 may not be involved in the regulatory process.
Leukemia 1994 Mar
PMID:The detection of colony-stimulating factors and steel factor in adherent layers of human long-term marrow cultures using reverse-transcriptase polymerase chain reaction. 751 Mar 57

In the present study the gene expression of cytokines promoting in vitro myeloma-cell growth was investigated by Northern blot analysis using total RNA of 36 tumour samples of patients with multiple myeloma (MM) or plasma cell leukaemia and poly(A)+ RNA of 10 human myeloma cell lines (HMCL). These cytokines included interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granulocyte-macrophage (GM)-colony-stimulating factor (CSF) and granulocyte (G)-CSF. IL-1 beta, IL-6 and G-CSF genes were coexpressed in most patients, although at variable levels. IL-1 alpha transcripts were detected in 32% of patients in whom coexpression of IL-1 beta gene was found. IL-3 gene was not expressed in patients' cells and GM-CSF mRNA was detected in only 1/32 patients. No detectable transcripts for the above cytokines were present in HMCL, whereas IL-6 gene was expressed in 2/10 HMCL. We also looked for the presence of transcripts for IL-2, leukaemia inhibitory factor (LIF) and transforming growth factor (TGF)beta in cells of tumour samples from the same patients and in HMCL. IL-2 gene was not expressed in MM patients and HMCL. Weak expression of LIF gene was detected in three patients (9%), and transforming growth factor beta (TGF beta) mRNA was observed in 12/12 tumour samples analysed and all HMCL. These results suggest that, among cytokines shown to control myeloma-cell growth in vitro, IL-1, IL-6 and G-CSF could play a role in the development of myeloma disease in vivo.
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PMID:Cytokine gene expression in human multiple myeloma. 751 Sep 89

An animal leukemia model was developed to investigate in vivo induction of differentiation of myeloid leukemia cells. An aneuploid cell line (C15) was isolated from mouse myelomonocytic leukemia WEHI-3B D+ cells. The C15 cells contained twice as much DNA as the parental cells but retained the morphology of myelomonocytic cells and the ability to differentiate into macrophage-like cells in response to all-trans retinoic acid (ATRA) in vitro. When the C15 cells were inoculated into the peritoneal cavity of syngeneic Balb/c mice (10(6) cells/mouse), the mice died of leukemia within 19 days. The DNA content and differentiation antigen (Mac-1) of the cells in the peritoneal cavity were determined by dual-parameter flow cytometry. On day 12 after inoculation, the C15 cells were distinguishable from normal host cells in the peritoneal cavity by their different DNA content. The administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (10 micrograms/day) to mice bearing C15 cells induced the leukemia cells to express Mac-1 antigen and to change morphologically into mature granulocytic cells. Because the C15 cells were not responsive to G-CSF in suspension culture in vitro, this result suggests that the cytokine's actions on the cells in vivo and in vitro are different. This experimental model for analyzing in vivo differentiation of leukemia cells will be useful for studying the therapeutic effects of potential differentiation-inducing agents.
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PMID:Flow-cytometric analysis of in vivo induction of differentiation of WEHI-3B myelomonocytic leukemia cells by recombinant granulocyte colony-stimulating factor. 751 48


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