1992 年度実績報告書

正常造血幹細胞,造血因子と造血器腫瘍との比較と相互関係

研究課題

研究課題/領域番号	04247105
研究機関	埼玉県立がんセンター
研究代表者	穂積本男埼玉県立がんセンター, 研究所, 所長 (50113478)
研究分担者	白川茂三重大学, 医学部, 教授 (20026850) 平井久丸東京大学, 医学部, 講師 (90181130) 斎藤政樹自治医科大学, 医学部, 教授 (60012762) 帯刀益夫東北大学抗酸菌病研究所, 細胞生物学部, 教授 (10099971) 大石道夫東京大学応用微生物学研究所, 教授 (00126004)
キーワード	D因子 / I因子 / Nm23 / NDPキナーゼ / リン酸化チロシン蛋白質 / c-myc遺伝子 / ガングリオシド / ltk蛋白質 / 受容体発現異常
研究概要	1.骨髄性白血病Ml細胞の糖鎖含有リコンビナントD因子投与がMl細胞移植マウスに対して延命効果を示した。また、各種サイトカイン(GM-CSF、インターフェロン、IL-4、IL-6)が活性型ビタミンD_3との併用で骨髄性白血病HL-60細胞や単球性白血病Mm細胞の増殖と分化を修飾することを明らかにした。他方、Ml細胞の分化誘導抑制因子(I因子)のアミノ酸配列は癌転移抑制遺伝子産物のNm23/NDPキナーゼと相同性のあることを発見した(穂積)。2.フレンド白血病細胞の分化誘導初期にリン酸化チロシン蛋白質レベルの減少が認められ、チロシンフォスファターゼの発現が分化誘導時に重要な役割を果たしていることを明らかにした(大石)。3.c-myc遺伝子がフレンド白血病細胞のβ-グロビンクロマチンにおけるDNase I hyper sensitive siteの発現を抑制していることを明らかにした(帯刀)。4.骨髄球系細胞分化の方向性の制御にガングリオシド(GM3)合成シアル酸転移酵素と、ネオラクト系ガングリオシド(Lc3Cer)合成N-アセチルグルコサミン転移酵素が必須であることを明らかにした(斎藤)。5.受容体型チロシンキナーゼヒトltk遺伝子の転写産物(蛋白質)を解析し、このltk蛋白質と会合し得るシグナル伝達物質がGTPase activating protein,phospholipaseC-γ,phosphatidylinositol-3-kinaseであることを見出した(平井)。6.各種急性白血病細胞に認められる諸種サイトカインの受容体発現異常を検討し、この受容体異常と臨床病態的、細胞学的特徴との関連性を明らかにした(白川)。

研究成果
(15件)

すべてその他

すべて文献書誌 (15件)

[文献書誌] Kasukabe,T.: "Characterization of growth inhibitory factors for mouse monocytic leukemia cells." Leukemia Res.16. 139-144 (1992)
[文献書誌] Okabe-Kado,J.: "Identity of a differentiation inhibiting factor for mouse myeloid leukemia cells with NM23/nucleoside diphosphate kinase." Biochem.Biophys.Res.Commun.182. 987-994 (1992)
[文献書誌] Yamomoto-Yamaguchi,Y.: "Prolongation by differentiation-stimulating factor/leukemia inhibitory factor of the survival time of mice implanted with mouse myeloid leukemia cells." Leukemia Res.16. 1025-1029 (1992)
[文献書誌] Nakamaki,T.: "The role granulocyte-macrophage colony-stimulating factor in induction of monocytic differentiation of HL-60cells:synergistic interaction with 1α,25-dihydroxyvitamin D_3 and interferon-γ in inducing interleukin-1β." Anticancer Res.12. 1331-1338 (1992)
[文献書誌] Kasukabe,T.: "Interleukin 4 potentiates the antiproliferative effect of 1α,25-dihydroxyvitamin D_3 on mouse monocytic leukemia cells but antagonizes the antiproliferative effects of interferon α,β and interleukin 6." Leukemia Res.16. 1191-1196 (1992)
[文献書誌] Chen,G.: "Effect of recombinant human D-factor on the growth of leukemic blast progenitors from acute myeloblastic leukemia patients." Jpn.J.Cancer Res.83. 1341-1346 (1992)
[文献書誌] Watanabe,T.: "Synergistic induction of erythroid differentiation of mouse erythroleukemia (MEL) cells by inhibitors of topoisomerases and protein tyrosine kinases." Exp.Cell Res.199. 269-274 (1992)
[文献書誌] Watanabe,T.: "Alteration of phosphotyrosine-containing proteins at the early stage of erythroid differentiation of mouse erythroleukemia (MEL) cells." J.Biol.Chem.267. 17116-17120 (1992)
[文献書誌] Takada,S.: "Overexpression of c-Myc inhibits the appearance of a specific DNase I hypersensitive site in the β-globin chromatin in murine erythroleukemia cells." Jpn.J.Cancer Res.82. 376-379 (1991)
[文献書誌] Nakamura,M.: "Total metabolic flow of glycosphingolipid biosynthesis is regulated by UDP-GlcNAc:lactosylceramideβ1→3N-acetylglu-cosaminyltransferase and CMP-NeuAc:lactosylceramideα2→3sialytransferase in human hematopoietic cell line HL-60 during differentiation." J.Biol.Chem.267. 23507-23514 (1992)
[文献書誌] Kozutsumi,H.: "Identification of the human ltk gene product in placenta and hematopoietic cell lines." Biochem.Biophys.Res.Commun.
[文献書誌] Toyoshima,H.: "Differently spliced cDNAs of human ltk receptor tyrosine kinase predict receptor proteins with and without tyrosire kinase domain and a soluble receptor protein." Proc.Natl.Acad.Sci.USA.
[文献書誌] Nakase,K.: "Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells." Brit.J.Haematol.80. 317-326 (1992)
[文献書誌] Nishii,K.: "c-kit gene expression in CD7-positive acute lymphoblastic leukemia:close correlation with expression of myeloid-associated antigen CD13." Leukemia. 6. 662-668 (1992)
[文献書誌] Kita,K.: "phenotypical characteristics of acute myelocytic leukemia associated with the t(8;21)(q22;q22) chromosomal abnormality:frequent expression of immature B-cell antigen CD19 together with stem cell antigen CD34." Blood. 80. 470-477 (1992)

1992 年度 実績報告書

正常造血幹細胞,造血因子と造血器腫瘍との比較と相互関係

研究代表者

穂積 本男 埼玉県立がんセンター, 研究所, 所長 (50113478)

研究成果

[文献書誌] Kasukabe,T.: "Characterization of growth inhibitory factors for mouse monocytic leukemia cells." Leukemia Res.16. 139-144 (1992)

[文献書誌] Okabe-Kado,J.: "Identity of a differentiation inhibiting factor for mouse myeloid leukemia cells with NM23/nucleoside diphosphate kinase." Biochem.Biophys.Res.Commun.182. 987-994 (1992)

[文献書誌] Yamomoto-Yamaguchi,Y.: "Prolongation by differentiation-stimulating factor/leukemia inhibitory factor of the survival time of mice implanted with mouse myeloid leukemia cells." Leukemia Res.16. 1025-1029 (1992)

[文献書誌] Nakamaki,T.: "The role granulocyte-macrophage colony-stimulating factor in induction of monocytic differentiation of HL-60cells:synergistic interaction with 1α,25-dihydroxyvitamin D_3 and interferon-γ in inducing interleukin-1β." Anticancer Res.12. 1331-1338 (1992)

[文献書誌] Kasukabe,T.: "Interleukin 4 potentiates the antiproliferative effect of 1α,25-dihydroxyvitamin D_3 on mouse monocytic leukemia cells but antagonizes the antiproliferative effects of interferon α,β and interleukin 6." Leukemia Res.16. 1191-1196 (1992)

[文献書誌] Chen,G.: "Effect of recombinant human D-factor on the growth of leukemic blast progenitors from acute myeloblastic leukemia patients." Jpn.J.Cancer Res.83. 1341-1346 (1992)

[文献書誌] Watanabe,T.: "Synergistic induction of erythroid differentiation of mouse erythroleukemia (MEL) cells by inhibitors of topoisomerases and protein tyrosine kinases." Exp.Cell Res.199. 269-274 (1992)

[文献書誌] Watanabe,T.: "Alteration of phosphotyrosine-containing proteins at the early stage of erythroid differentiation of mouse erythroleukemia (MEL) cells." J.Biol.Chem.267. 17116-17120 (1992)

[文献書誌] Takada,S.: "Overexpression of c-Myc inhibits the appearance of a specific DNase I hypersensitive site in the β-globin chromatin in murine erythroleukemia cells." Jpn.J.Cancer Res.82. 376-379 (1991)

[文献書誌] Kozutsumi,H.: "Identification of the human ltk gene product in placenta and hematopoietic cell lines." Biochem.Biophys.Res.Commun.

[文献書誌] Toyoshima,H.: "Differently spliced cDNAs of human ltk receptor tyrosine kinase predict receptor proteins with and without tyrosire kinase domain and a soluble receptor protein." Proc.Natl.Acad.Sci.USA.

[文献書誌] Nakase,K.: "Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells." Brit.J.Haematol.80. 317-326 (1992)

[文献書誌] Nishii,K.: "c-kit gene expression in CD7-positive acute lymphoblastic leukemia:close correlation with expression of myeloid-associated antigen CD13." Leukemia. 6. 662-668 (1992)

[文献書誌] Kita,K.: "phenotypical characteristics of acute myelocytic leukemia associated with the t(8;21)(q22;q22) chromosomal abnormality:frequent expression of immature B-cell antigen CD19 together with stem cell antigen CD34." Blood. 80. 470-477 (1992)

1992 年度実績報告書

穂積本男埼玉県立がんセンター, 研究所, 所長 (50113478)