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Pirjo Koistinen – 1st expert on this subject based on the ideXlab platform
The soluble form of interleukin-6 receptor modulates Cell proliferation by acute myeloBlastic leukemia Blast Cells.Annals of Hematology, 1999Co-Authors: Marjaana Säily, Pirjo Koistinen, Eevariitta SavolainenAbstract:
As interleukin-6 (IL-6) has been shown to have diverse effects on Blast Cell growth in acute myeloBlastic leukemia (AML), and as a soluble (s) form of IL-6 receptor (IL-6R) agonizes IL-6 effects in many Cell types, we investigated whether sIL-6R was able to modulate clonogenic Blast Cell growth in AML. The proliferation responses of eight autonomously growing AML Cell lines and eight primary AML Blast Cell samples were compared with their IL-6 and sIL-6R expression. Only three of the 16 AML samples were influenced by IL-6, two of them being stimulated and one inhibited by it. The sIL-6R-induced responses were more frequent, however, and, in contrast to those by IL-6, always stimulatory: clonogenic Cell growth in six of the 16 AML samples was stimulated by sIL-6R treatment. All the Cell lines and four of the seven primary Blast Cell samples analyzed expressed IL-6, and the expression was associated with unresponsiveness to exogenous IL-6. sIL-6R was also frequently expressed by AML Cells: only one of the samples was negative for it. However, there was no correlation between sIL-6R expression and the responsiveness of Cells to exogenous sIL-6R. The work presented here shows that sIL-6R is able to stimulate Blast Cell growth in AML. As AML Blast Cells are provided by exogenous IL-6 and sIL-6R in a bone marrow environment, and as many of them also express IL-6 and sIL-6R themselves in vitro, it is possible that signaling through the IL-6/sIL-6R system plays a role in maintaining their growth also in vivo.
effect of mast Cell growth factor on clonogenic Blast Cell growth in acute myelogenous leukemiaAnnals of Hematology, 1996Co-Authors: Timo Siitonen, M Lundstrom, Aiping Zheng, Eevariitta Savolainen, Pirjo KoistinenAbstract:
The effect of the mast Cell growth factor (MGF), also known as stem Cell factor, steel factor, and kit ligand, alone or in combination with other GFs on clonogenic Blast Cell growth in 23 patients with acute myeloBlastic leukemia (AML) was investigated. MGF alone enhanced colony formation by about 35%, being clearly stimulatory (>20% increase in colony numbers) in nine patients. The additive effect of MGF on colony growth was observed in combination with interleukin-3 (IL-3). Preincubation of the Cells with MGF in suspension did not sensitize them to the effect of IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, or IL-4 in a clonogenic Cell culture assay. Although almost all the Blast Cell samples expressed the c-kit the receptor for MGF, at the mRNA and/or the protein level, the Cells did not necessarily respond to exogenous MGF. On the other hand, Blast Cells were able to respond to exogenous MGF even when the Cells themselves expressed MGF. Neither the expression of MGF nor the response of Blast Cells to exogenous MGF was related to the capability of the Cells to form colonies spontaneously. In conclusion, MGF alone, but especially combined with IL-3, was a potent growth factor for clonogenic Blast Cells in AML. Autocrine production of MGF by AML Blast Cells analyzed at the mRNA level was not related to autonomous growth of the Cells.
D Metcalf – 2nd expert on this subject based on the ideXlab platform
lineage commitment of hemopoietic progenitor Cells in developing Blast Cell colonies influence of colony stimulating factorsProceedings of the National Academy of Sciences of the United States of America, 1991Co-Authors: D MetcalfAbstract:
In clonal cultures of normal mouse marrow Cells, combination of granulocyte, granulocyte-macrophage, or multipotential colony-stimulating factor (G-CSF, GM-CSF, or multi-CSF, respectively) with stem Cell factor (SCF) did not alter the number of Blast colonies stimulated to develop compared with SCF alone but induced an up to 25-fold increase in their mean Cell content and an up to 6-fold increase in their mean progenitor Cell content. Costimulation of Blast colony formation by SCF plus G-CSF did not change the relative frequency of progenitor Cells of different types within the colonies compared with colonies stimulated by SCF alone. However, combination of GM-CSF or multi-CSF with SCF significantly increased the relative frequency of granulocytic progenitors and, for multi-CSF, also of eosinophil progenitor Cells. These changes in the relative frequencies of progenitor Cells committed to the various lineages support the hypothesis that hemopoietic regulators have some ability to induce selective lineage commitment in the progeny of multipotential Cells.
Makio Ogawa – 3rd expert on this subject based on the ideXlab platform
enhancement of murine Blast Cell colony formation in culture by recombinant rat stem Cell factor ligand for c kitBlood, 1991Co-Authors: K Tsuji, K M Zsebo, Makio OgawaAbstract:
Mice with W mutations characterized by hypopigmentation, sterility, anemia, and mast Cell deficiency have abnormalities in c-kit, a receptor with tyrosine kinase activity. Recently, the ligand for c-kit was cloned by investigators in several laboratories. Zsebo et al identified and cloned a gene for a cytokine termed stem Cell factor (SCF) in the medium conditioned by buffalo rat liver Cells, and this cytokine proved to be c-kit ligand. We have examined the effects of recombinant rat SCF (rrSCF) on colony formation from primitive hematopoietic progenitors in culture. rrSCF and erythropoietin (Ep) supported formation of granulocyte/macrophage (GM) colonies as well as a small number of multilineage and Blast Cell colonies from marrow Cells of normal mice. We then examined the effects of rrSCF using marrow and spleen Cells of mice that had been treated with 150 mg/kg 5- fluorouracil (5-FU). Unlike single factors, combinations of factors such as rrSCF plus interleukin-3 (IL-3), rrSCF plus IL-6, and rrSCF plus granulocyte colony-stimulating factor (G-CSF) markedly stimulated the growth of multilineage colonies. In contrast to these factor combinations and a combination of IL-3 and IL-6, a combination of rrSCF and IL-4 did not support multilineage colony formation. Mapping studies of the development of multipotential Blast Cell colonies further indicated that rrSCF, like IL-6, G-CSF, and IL-11, shortens the dormant period in which the stem Cells reside. When we tested the effects of rrSCF using pooled Blast Cells, which are highly enriched for progenitors and are devoid of stromal Cells, rrSCF plus Ep supported formation of only a few multilineage colonies, indicating that rrSCF itself is ineffective in support of the proliferation of multipotential progenitors. However, rrSCF supported formation of a significant number of neutrophil and neutrophil/macrophage colonies from pooled Blast Cells, indicating that rrSCF is able to support directly the proliferation of progenitors in neutrophil/monocyte lineages. c-kit ligand may play important roles in adult hematopoiesis.