1991 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	03252105
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) 渡辺利雄東京大学, 応用微生物学研究所, 助手 (60201208)
キーワード	分化誘導因子 / フレンド白血病細胞 / チロシンキナ-ゼ / cーmyc遺伝子 / ガングリオシド / ltk遺伝子 / 幹細胞性白血病 / プロティンキナ-ゼC
研究概要	1.骨髄性白血病M1細胞の分化誘導因子(D因子)は、テラトカルシノ-マF9細胞の分化誘導抑制作用および骨芽細胞の骨吸収作用のあることを見出した。また、インタ-フェロンβ,ILー4、ILー6は単球性白血病細胞の増殖と分化を著しく修飾することを認めた(穂積)。 2.フレンド白血病細胞の分化誘導に関与するチロシンキナ-ゼはEGF受容体チロンキナ-ゼ様であることを明らかにし、燐酸化チロシンホスファタ-ゼ活性の低下と分化誘導能とが密接に関連していることを明らかにした(大石)。 3.cーmyc遺伝子がフレンド白血病細胞の転写因子として機能していることを証明し、cーmycが細胞増殖、分化の転換を制御していることを示唆した(帯刀)。 4.シアロ糖脂質ガングリオシド(GM_3、2‐3sialosylparagloboside(SPG)の各種ヒト白血病細胞に対する分化誘導と増殖抑制効果を明らかにし、その作用機序を検討した(斎藤)。 5.ヒト胎盤cDNAライブラリ-より、正常ヒトltk遺伝子を単離してその構造を解析し、ltk遺伝子の翻訳開始点、遺伝子産物、コ-ディング領域を明らかにした(平井)。 6.白血病細胞の表現型、遺伝子型、染色体、増血因子に対する反応性などの解析から幹細胞性白血病が従来の想定より高頻度に存在しており、特定の形質発現の異常から診断可能であることを明らかにした。また、白血病の細胞種、白血病細胞の分化段階の差違によってプロティンキナ-ゼCアイソザイムの発現が異なることを見出した(白川)。

研究成果

(22件)

すべてその他

すべて文献書誌 (22件)

[文献書誌] Hirayoshi,K.: "Both DーFactor/LIF and ILー6 inhibit the differentiation of mouse teratocarcinoma F9 cells" FEBS Letters. 282. 401-404 (1991)
[文献書誌] Kasukabe,T.: "Interleukin 4 inhibits the differentiation of mouse myeloid leukemia M1 cells induced by dexamethasone,Dーfactor/Leukemia inhibitory factor and interleukinー6,but not by 1α,25ーdihydroxyvitamin D_3" FEBS Letters. 291. 181-184 (1991)
[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] Ishimi,Y.: "Leukemia inhibitory factor/differentiation stimulating factor (LIF/Dーfactor):regulation of its production and possible roles in bone" J.Cell.Physiol.(1992)
[文献書誌] Watanabe,T.: "Induction of in vitro differentiation of mouse erythroleukemia (MEL) cells by genistein,an inhibitor for tyrosine protein kinases" Cancer Res.51. 764-768 (1991)
[文献書誌] Kondo,K.: "Induction of in vitro differentiation of mouse embryonal carcinoma (F9) cells by inhibitors of topoisomerases" Cancer Res.51. 5398-5404 (1991)
[文献書誌] Watanabe,T.: "Synergistic induction of mouse erythroleukemia (MEL) cells by inhibitors of topoisomerases and protein tyrosine kinases" Exp.Cell Res.(1992)
[文献書誌] Takada,S.: "Overexpression of cーMyc inhibits the appearance of a specific DNase I hypersensitive site in the βーglobin chromatin in murine erythroleukemia cells" Jpn.J.Cancer Res.82. 376-379 (1991)
[文献書誌] Takada,S.: "cーMyc interferes with the commitment of differentiation of murine erythroleukemia cells at a reversible point" Jpn.J.Cancer Res.(1992)
[文献書誌] Nakamura,M.: "Radioimmune assay of sialyltransferase and Nーacetylーgalactosaminyltransferase activities using specific antibodies on a 96ーwell filtration plate of a multiscreen assay system" Anal.Biochem.198. 154-159 (1991)
[文献書誌] Nakamura,M.: "Ganglioside GM3 can induce megakaryocytoid differentiation of human leukemia cell line K562 cells" Cancer Res.51. 1940-1945 (1991)
[文献書誌] Hirai,H.: "Analysis of Ph1ーpositive leukemia by PCR" Jpn.Clinical Hematol.32. 319-326 (1991)
[文献書誌] Maru,Y.: "Human ltk:gene structure and preferential expression in human leukemic cells" Oncogene Res.5. 199-204 (1990)
[文献書誌] Komada,F.: "Expression of three major protein kinase C isozymes in various types of human leukemic cells" Cancer Res.51. 4271-4278 (1991)
[文献書誌] Nakase,K.: "Diagnositc and clinical importance of interleukinー2 receptor alpha chain expression on nonーTーcell acute leukemia cells" Br.J.Haematol.(1992)
[文献書誌] Nishii,K.: "cーkit gene expression in CD7ーpositive acute lymphoblastic leukemia:a close correlation with expression of myeloid associated antigen CD13" Leukemia. (1992)
[文献書誌] Kawakami,K.: "Rearrangement pattern of immunoglobulin heavy chain (IgH) and light chain genes in acute lymphoblastic leukemia and chronic myelocytic leukemia lymphoid crisis cells showing oligoclonal IgH gene rearrangements" Int.J.Hematol.(1992)
[文献書誌] Hozumi,M.: "The Status of Differentiation Therapy of Cancer,Vol.II" Raven Press,New York,U.S.A., 7 (1991)
[文献書誌] Hozumi,M.: "The Status of Differentiation Therapy of Cancer,Vol.II" Raven Press,New York,U.S.A., 10 (1991)
[文献書誌] Watanabe,T.: "The Status of Differentiation Therapy of Cancer,Vol.II" Raven Press,New York,U.S.A., 11 (1991)
[文献書誌] Saito,M.: "The Status of Differentiation Therapy of Cancer,Vol.II" Raven Press,New York,U.S.A., 7 (1991)
[文献書誌] Shimizu,N.: "Myelodysplastic syndrome and cytokines" Excerpta Medica,Amsterdam, 4 (1991)

1991 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] Hirayoshi,K.: "Both DーFactor/LIF and ILー6 inhibit the differentiation of mouse teratocarcinoma F9 cells" FEBS Letters. 282. 401-404 (1991)

[文献書誌] Kasukabe,T.: "Interleukin 4 inhibits the differentiation of mouse myeloid leukemia M1 cells induced by dexamethasone,Dーfactor/Leukemia inhibitory factor and interleukinー6,but not by 1α,25ーdihydroxyvitamin D_3" FEBS Letters. 291. 181-184 (1991)

[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] Ishimi,Y.: "Leukemia inhibitory factor/differentiation stimulating factor (LIF/Dーfactor):regulation of its production and possible roles in bone" J.Cell.Physiol.(1992)

[文献書誌] Watanabe,T.: "Induction of in vitro differentiation of mouse erythroleukemia (MEL) cells by genistein,an inhibitor for tyrosine protein kinases" Cancer Res.51. 764-768 (1991)

[文献書誌] Kondo,K.: "Induction of in vitro differentiation of mouse embryonal carcinoma (F9) cells by inhibitors of topoisomerases" Cancer Res.51. 5398-5404 (1991)

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

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

[文献書誌] Takada,S.: "cーMyc interferes with the commitment of differentiation of murine erythroleukemia cells at a reversible point" Jpn.J.Cancer Res.(1992)

[文献書誌] Nakamura,M.: "Radioimmune assay of sialyltransferase and Nーacetylーgalactosaminyltransferase activities using specific antibodies on a 96ーwell filtration plate of a multiscreen assay system" Anal.Biochem.198. 154-159 (1991)

[文献書誌] Nakamura,M.: "Ganglioside GM3 can induce megakaryocytoid differentiation of human leukemia cell line K562 cells" Cancer Res.51. 1940-1945 (1991)

[文献書誌] Hirai,H.: "Analysis of Ph1ーpositive leukemia by PCR" Jpn.Clinical Hematol.32. 319-326 (1991)

[文献書誌] Maru,Y.: "Human ltk:gene structure and preferential expression in human leukemic cells" Oncogene Res.5. 199-204 (1990)

[文献書誌] Komada,F.: "Expression of three major protein kinase C isozymes in various types of human leukemic cells" Cancer Res.51. 4271-4278 (1991)

[文献書誌] Nakase,K.: "Diagnositc and clinical importance of interleukinー2 receptor alpha chain expression on nonーTーcell acute leukemia cells" Br.J.Haematol.(1992)

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

[文献書誌] Kawakami,K.: "Rearrangement pattern of immunoglobulin heavy chain (IgH) and light chain genes in acute lymphoblastic leukemia and chronic myelocytic leukemia lymphoid crisis cells showing oligoclonal IgH gene rearrangements" Int.J.Hematol.(1992)

[文献書誌] Hozumi,M.: "The Status of Differentiation Therapy of Cancer,Vol.II" Raven Press,New York,U.S.A., 7 (1991)

[文献書誌] Hozumi,M.: "The Status of Differentiation Therapy of Cancer,Vol.II" Raven Press,New York,U.S.A., 10 (1991)

[文献書誌] Watanabe,T.: "The Status of Differentiation Therapy of Cancer,Vol.II" Raven Press,New York,U.S.A., 11 (1991)

[文献書誌] Saito,M.: "The Status of Differentiation Therapy of Cancer,Vol.II" Raven Press,New York,U.S.A., 7 (1991)

[文献書誌] Shimizu,N.: "Myelodysplastic syndrome and cytokines" Excerpta Medica,Amsterdam, 4 (1991)

1991 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)