Modulation of GM-CSF Receptor β-subunit and Interleukin-6 Receptor mRNA Expression in a Human Megakaryocytic Leukemia Cell Line

1992 ◽  
Vol 8 (4-5) ◽  
pp. 397-403 ◽  
Author(s):  
Mutsumi Yasunaga ◽  
Ryukichi Ryo ◽  
Nobuo Yamaguchi
Keyword(s):  
Mrna Expression ◽  
Cell Line ◽  
Interleukin 6 ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Β Subunit ◽  
Gm Csf ◽  
Receptor Mrna ◽  
Interleukin 6 Receptor

scholarly journals An increase in the expression and total activity of endogenous p60c-Src in several factor-independent mutants of a human GM-CSF-dependent leukemia cell line (TF-1)

Oncogene ◽  
2003 ◽  
Vol 22 (46) ◽  
pp. 7170-7180 ◽  
Author(s):  
Stefan Horn ◽  
Johann Meyer ◽  
Carol Stocking ◽  
Wolfram Ostertag ◽  
Manfred Jücker
Keyword(s):  
Cell Line ◽  
Leukemia Cell ◽  
Total Activity ◽  
Leukemia Cell Line ◽  
Gm Csf

Human Plasmacytoid Dendritic Cell like Leukemia Cell Line (PMDC05) Established from a Patient with CD4+CD56+ Acute Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4456-4456
Author(s):  
Miwako Narita ◽  
Nozomi Tochiki ◽  
Norihiro Watanabe ◽  
Anri Saitoh ◽  
Shigeo Hashimoto ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cell ◽  
Acute Leukemia ◽  
Cell Line ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Type I ◽  
Gm Csf ◽  
Antigen Presenting

Abstract Human dendritic cell precursors are commonly divided into two distinct subsets: myeloid DC and Plasmacytoid DC (pDC). The pDC, which show plasma cell like morphology, have been defined as the population that produce a large amount of type I interferon in response to viruses. The surface phenotypes of human pDCs are defined as CD4+, DC11c−, CD45RA+, IL3Rα (CD123)+, CD1c (BDCA-1)−, CD303 ((BDCA-2)+ and lineage negative. On the other hand, leukemia/lymphoma cells in CD4+CD56+ leukemia/lymphoma have been proposed to be of pDC lineage. CD4+CD56+ pDC leukemia/lymphoma are a rare hematological malignancy, totally only about 100 cases in the world by the literatures. We established a pDC like leukemia cell line (PMDC05) from leukemia cells of a patient with CD4+CD56+ acute leukemia. PMDC05 showed a complex hypoploid chromosomal abnormalities (44, XY) including add(5)(q22), add(15)(q26) and del(15)(q11q15), which is identical to original leukemia cells. Abnormalities including 5q and 15q are reported as the frequent aberrations in CD4+CD56+ pDC leukemia/lymphoma. PMDC05, which morphology was similar to plasma cells, was positive for CD4, CD56, CD123, CD33, CD86, HLA-ABC, HLA-DR, CD1a, CD40, and CD83 but negative for linage markers. Cytokine receptors for GM-CSF, IL3Rα and IL-6Rα were positive on PMDC05. The expression of Trail and Flt-3L was positive. By the culture with IL-3, CPG-A/B, GM-CSF, molecules associated with antigen presentation such as CD1a and CD40 were up-regulated. Besides, the addition of LPS increased the expression of CD40, CD80 and CD83 on PMDC05. PMDC05 by itself possessed a potent antigen presenting ability to naïve T cells and the treatment of PMDC05 with IL-3, CPG-A/B, or GM-CSF enhanced the antigen presenting ability to naïve T cells. TLR7, TLR 8 and TLR 9 as well as TLR1, TLR2, TLR4 were demonstrated to be expressed on PMDC05 by RT-PCR and RQ-PCR showed that the expression of TLR7 and TLR9 was most characteristic. λ-like 14.1 and preTα was also demonstrated to be expressed on PMDC05 by RT/RQ-PCR. PMDC05 possessed an ability to uptake the antigens like FITC-dextran and lucifer yellow. Although IFN-α was not identified to be secreted from PMDC05 by the stimulation of influenza virus, IFN-γ and TNF-α was demonstrated to be secreted to the similar level in pDC, which was examined simultaneously with PMDC05 by CBA assay. These data demonstrated that newly established leukemia cell line PMDC05 is involved in pDC lineage and PMDC05 provides invaluable tools not only for the elucidation of pathophysiology of CD4+CD56+ leukemia/lymphoma but also for the investigation of differntiation and regulation of pDC. In addition, PMDC05 could be applied for generating tumor-specific CTL clone, which may be used for anti-tumor cellular immunotherapy.

Optimization of a BCR-ABL-Specific DNA Vaccine against Ph+ ALL Using a Nonviral Vector System and Nanoparticle Delivery

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4625-4625
Author(s):  
Yvonne Rott ◽  
Stefanie Arndt ◽  
Jordan Green ◽  
Daniel Anderson ◽  
Renata Stripecke ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Cell Line ◽  
Dna Vaccine ◽  
Cd8 T Cells ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Gm Csf

Abstract Although 40–50% of adults and 70–80 % of children with acute lymphoblastic leukemia (ALL) can be cured by poly chemo therapy, the prognosis of patients with Philadelphia chromosome positive (Ph+) ALL remains poor. Therefore, new relapse prevention strategies are needed for patients with Ph+ ALL during remission. We have shown previously, that vaccination of mice with leukemia cell lines modified to express costimulatory molecules and cytokines induce a systemic immunity against the syngeneic BCR-ABLp185 expressing leukemia cell line BM185. However, the difficulties to culture and transfect human leukemia cells limit the clinical application of leukemia cell based vaccines. Thus, we evaluated the immunization of mice with DNA-based vaccines subsequently challenged by the cell line BM185. Combinations of minimalistic immunogenically defined gene expression (MIDGE) vectors encoding a BCR-ABLp185 fusion specific peptide, GM-CSF, IL12, IL27 or CD40L were used for in vivo transfection of murine skin. In addition, we used natural DNA-based double stem-loop immunomodulators (dSLIM), containing three CpG-motifs as non-specific immune adjuvant. In order to increase transfection efficacy, MIDGE-vectors were microencapsulated into poly(β-aminoester) nanoparticles with diameters of 200 nm. Mice immunized with the BCR-ABL/GM-CSF/dSLIM vaccine showed a significant longer mean tumor-free (p=0.019) and overall survival (p=0.008) compared to nonvaccinated mice. BCR-ABL specific sequences were required to prevent Ph+ acute lymphoblastic leukemia. Furthermore, CTL assays showed that specific lysis was significantly higher after vaccination with BCR-ABL/GM-CSF/dSLIM compared to GMCSF/dSLIM (p<0.05) and to naïve mice (p<0.005). The vaccine efficacy was clearly dosedependent. Microencapsulation of MIDGE vectors increased the efficacy of the vaccine compared to the naked DNA-vaccine. Mice immunized with the microencapsulated vaccine BCR-ABL/GM-CSF/dSLIM showed a significant longer mean tumor-free (p<0.0001) and overall survival (p<0.0001) compared to non-vaccinated mice and 70% survived and never developed leukemia. Cotransfection with IL27 or IL12 lead to significant longer tumor free (IL27: p=0.02; IL12: p<000.1) and overall survival (IL-27: p=0.03; IL12: p<000.1) compared to the vaccine BCR-ABL/GM-CSF/dSLIM. The best protection with a survival rate of 91% was observed in mice which received the vaccine BCR-ABL/GMCSF/IL12/dSLIM. We have shown previously in T-cell depletion studies that CD8+ T cells were the effector cells in the BM185 cell-based vaccine model and currently we evaluate whether CD8+ T cells also play a major role in the BM185 DNA-based vaccine model. In conclusion, we provide survival and functional data that show immunization and protection of mice with optimized leukemia specific DNA-vaccines.

scholarly journals Characterization of the cell surface receptor for human granulocyte/macrophage colony-stimulating factor.

1986 ◽  
Vol 164 (1) ◽  
pp. 251-262 ◽  
Author(s):  
L S Park ◽  
D Friend ◽  
S Gillis ◽  
D L Urdal
Keyword(s):  
Cell Line ◽  
Leukemia Cell ◽  
Cell Types ◽  
Myelogenous Leukemia ◽  
Cell Surface Receptor ◽  
Leukemia Cell Line ◽  
Human Neutrophils ◽  
Binding Studies ◽  
Single Class ◽  
Gm Csf

125I-labeled recombinant human GM-CSF was used to identify and characterize receptors specific for this lymphokine on both a mature primary cell, human neutrophils, and on the undifferentiated promyelomonocytic leukemia cell line, HL-60. Human GM-CSF also bound to primary human monocytes and to the myelogenous leukemia cell line, KG-1, but not to any of the murine cells known to express the murine GM-CSF receptor. In addition, although some murine T lymphomas can express the GM-CSF receptor, none of the human cell lines of T cell lineage that we examined bound iodinated human GM-CSF. Binding to all cell types was specific and saturable. Equilibrium binding studies revealed that on all cell types examined, GM-CSF bound to a single class of high affinity receptor (100-500 receptors per cell) with a Ka of 10(9)-10(10)/M. More extensive characterization with neutrophils and HL-60 cells showed that in both cases, binding of GM-CSF was rapid at 37 degrees C with a slow subsequent dissociation rate that exhibited marked biphasic kinetics. Among a panel of lymphokines and growth hormones, only human GM-CSF could compete for binding of human 125I-GM-CSF to these cells. GM-CSF can not only stimulate the proliferation and differentiation of granulocyte/macrophage precursor cells, but can modulate the functional activity of mature granulocytes and macrophages as well. No significant differences in the kinetic parameters of receptor binding were seen between mature neutrophils and the undifferentiated promyelocytic leukemia cell line HL-60, indicating that maturation-specific responses to GM-CSF are not mediated by overt changes in the binding characteristics of the hormone for its receptor.

scholarly journals Establishment and characterization of a new human leukemia cell line derived from M4E0

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 451-457 ◽  
Author(s):  
K Yanagisawa ◽  
T Horiuchi ◽  
S Fujita
Keyword(s):  
Protein Kinase C ◽  
Cell Line ◽  
Colony Formation ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Human Leukemia ◽  
Gm Csf ◽  
Kinase C ◽  
Proliferation And Differentiation ◽  
Human Leukemia Cell Line

A new human leukemia cell line, designated as ME-1, was established from the peripheral blood leukemia cells of a patient with acute myelomonocytic leukemia with eosinophilia (M4E0). This cell line has the characteristic chromosome abnormality of M4E0, inv(16) (p13q22). When cultured in RPMI 1640 medium containing 10% fetal calf serum, ME-1 cells were monoblastoid, but with the addition of cytokines such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, or medium conditioned by phytohemagglutinin-stimulated human peripheral leukocytes (PHA-LCM), the cells exhibited differentiation to macrophage-like cells. PHA-LCM also promoted eosinophilic-lineage differentiation of this cell line, although IL-5 did not do so. To elucidate the mechanism of proliferation and differentiation of ME-1 cells, we studied the effect of a potent inhibitor of protein kinase C, 1-(5-isoquinolinyl-sulfonyl)-2- methylpiperazine (H-7), on colony formation of ME-1 cells. H-7 inhibited colony formation of ME-1 cells by IL-3 or GM-CSF dose dependently, but had little inhibitory effect on colony formation by IL- 4. These results indicate that the proliferation and differentiation of ME-1 cells by IL-3 or GM-CSF were related to the activation of protein kinase C, while those by IL-4 involved other regulatory systems. ME-1 cells should be useful for studying the pathogenesis of M4E0 and the mechanisms of proliferation and differentiation of leukemic and normal progenitors by cytokines.

scholarly journals Establishment of a human acute myeloid leukemia cell line (Kasumi-1) with 8;21 chromosome translocation

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 2031-2036 ◽  
Author(s):  
H Asou ◽  
S Tashiro ◽  
K Hamamoto ◽  
A Otsuji ◽  
K Kita ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Chromosome Translocation ◽  
Leukemia Cell Line ◽  
Gm Csf ◽  
Human Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract A novel leukemic cell line with an 8;21 chromosome translocation, designated as Kasumi-1, was established from the peripheral blood of a 7-year-old boy suffering from acute myeloid leukemia (AML). The Kasumi- 1 cells were positive for myeloperoxidase showing a morphology of myeloid maturation. The response in proliferation assay was observed in the culture with interleukin-3 (IL-3), IL-6, granulocyte colony- stimulating factor (G-CSF), and granulocytemacrophage CSF (GM-CSF), but not with IL-1 or IL-5. Neither granulocytic nor eosinophilic maturation was observed in the liquid culture by the addition of dimethyl sulfoxide, G-CSF, or IL-5, respectively. In contrast, induction of macrophagelike cells was seen by the addition of phorbol ester. This is the first report of a human AML cell line with t(8;21) that has characteristics of myeloid and macrophage lineages. The cell line could be a useful tool for elucidating the pathophysiology of AML with t(8;21).

scholarly journals In Vitro Development of Erythroid and Megakaryocytic Cells From a UT-7 Subline, UT-7/GM

Blood ◽  
1997 ◽  
Vol 89 (11) ◽  
pp. 4021-4033 ◽  
Author(s):  
Norio Komatsu ◽  
Keita Kirito ◽  
Ritsuko Shimizu ◽  
Masae Kunitama ◽  
Minami Yamada ◽  
...  
Keyword(s):  
Cell Line ◽  
Leukemia Cell ◽  
Hemoglobin Concentration ◽  
Erythroid Differentiation ◽  
Leukemia Cell Line ◽  
Mrna Levels ◽  
Platelet Factor ◽  
Megakaryoblastic Leukemia ◽  
Gm Csf

Abstract UT-7 is a human megakaryoblastic leukemia cell line with absolute dependence on interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF ), or erythropoietin (EPO) for growth and survival. We isolated a novel subline, UT-7/GM after long-term culture of UT-7 with GM-CSF. The hemoglobin concentration and γ-globin and EPO-receptor mRNA levels were significantly higher in EPO-treated UT-7/GM cells than in untreated cells. In contrast, the platelet factor 4 and glycoprotein IIb mRNA levels were much higher in thrombopoietin (TPO)-treated UT-7/GM cells than in untreated cells. Some TPO-treated cells had morphologically mature megakaryocytic characteristics such as a developed demarcation membrane in the cytoplasm and multilobular nuclei. These findings indicate that UT-7/GM is a bipotential cell line that can be induced to differentiate into erythroid and megakaryocytic lineages by EPO and TPO, respectively. Moreover, a minority of UT-7/GM cells acquired a high hemoglobin concentration by treatment with TPO, suggesting that TPO in part induced the erythroid differentiation of the UT-7/GM cells. Interestingly, GM-CSF inhibited the EPO- or TPO-induced erythroid differentiation and the TPO-induced megakaryocytic differentiation of UT-7/GM cells. These results support the hypothesis that cytokines influence the programming of gene expression required for lineage commitment or differentiation.

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