| Project/Area Number |
63440044
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | The Institute of Medical Science, The University of Tokyo (IMSUT) |
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Principal Investigator |
ASANO Shigetaka Imsut, Professor., 医科学研究所, 教授 (50134614)
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| Co-Investigator(Kenkyū-buntansha) |
TOJO Arinobu Imsut, Research Associate., 医科学研究所, 助手 (00211681)
TANI Kenzabro Imsut, Lecturer., 医科学研究所, 講師 (00183864)
OZAWA Keiya Imsut, Associate Professor., 医科学研究所, 助教授 (30137707)
SATO Noriharu Imsut, Asoociate Professor., 医科学研究所, 助教授 (90162461)
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| Project Period (FY) |
1988 – 1990
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| Keywords | Granulocyte colony-stimulating factor, / Acute Myelogenous leukemia, / Intracellular signal transduction / 02Receptor for granulocyte colony-stimulating factor, |
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| Research Abstract |
G-CSF is a physiological glycoprotein capable specifically stimulation of the proliferation and differentiation from stem cells to neutrophils as well as activating the functions of nature meutrophils. Therefore it is of great interest to investigate whether or not and how G-CSF might act on acute myelogenous leukemia cells characteristically associated with maturation block. Most of acute myelogenous leukemia cells were shown to proliferate but not to differentiate following the specifical binding of G-CSF. It was also demonstrated in some typical myelogenous leukemia cells that G-CSF induces the activation of the GTP binding proteins/adenylate cyclase system, the increase of intracellular Ca^<++>, the translocation of protein kinase C, the increased expression of ALP and hck mRNAs, and the decreased expression of MPO and myc mRNAs. However, we could not show any clear differences in these parameters between normal and leukemia cells. For further investigation we attempted to characterize the G-CSF receptors (G-CSFR) as well as the G-CSF responsive genes of the myeloid leukemia cells. As for the G-CSFR, Dr. Nagata's group (Osaka Bioscience Institute) had successfully purified G-CSFR and cloned its cDNA. Then we investigated the expression of G-CSFR mRNA in various human leukemia cells in collaboration with his group. The results to date have been compatible with those which we obtained from the binding study. Based on these data, we are now analyzing whether or not there might be any abnormalities at the DNA levels in the leukemia cells. As for the G-CSF responsive genes, on the other hand, we have recently succeeded in constructing the cDNA library using the leukemia cells stimulated with or without G-CSF. We expect that further studies in this area might be important to identify new genes responsible to the maturation block characteristic of acute myelogenous leukemia cells.
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