1996 Fiscal Year Annual Research Report

サイトカインを介した造血幹細胞の増殖と分化の制御機構の解析

Research Project

Project/Area Number	08261211
Research Institution	Kyushu University
Principal Investigator	仁保喜之九州大学, 医学部, 教授 (60091287)
Co-Investigator(Kenkyū-buntansha)	浅野嘉延九州大学, 医学部, 助手 (60271110) 岡村精一九州大学, 医学部, 講師 (20136435)
Keywords	G-CSF / G-CSF受容体 / 先天性好中球減少症 / 骨髄性白血病 / 遺伝子発現 / 点突然変異
Research Abstract	造血異常症におけるG-CSF受容体の解析を行った。先天性好中球減少症の一例において、直前のintronの点突然変異によるsplicing異常により、細胞内領域の最初の3塩基が欠失しているG-CSF受容体の構造異常を発見した。G-CSF受容体の膜貫通部近傍は細胞増殖シグナルに関連する領域であり、本症例の骨髄細胞は試験管内でG-CSFに対する増殖反応性が著しく低下していた。そこで、このG-CSF受容体の構造異常が病因となり得る可能性を考え、発現実験を行った。正常G-CSF受容体を遺伝子発現させたIL-3依存株のBa/F3細胞はG-CSF存在下で経時的に細胞数が増加したが、本症例で認めた変異G-CSF受容体を発現させた細胞は増加しなかった。トリチウムチミジンの取り込み率でも、正常G-CSF受容体を発現させた細胞と異なり、変異G-CSF受容体を発現させた細胞はG-CSF添加による取り込み率の増加を認めなかった。以上の結果より、我々の発見したG-CSF受容体の構造異常が、本症例における好中球系細胞の増殖障害を引き起こしている可能性が強く示唆された。我々は、この症例以外にも、G-CSF受容体の細胞内領域に構造異常を有する先天性好中球減少症患者を発見し、病的意義を解析中である。さらに、急性骨髄性白血病41例、骨髄異形成症候群9例、慢性骨髄性白血病20例において、G-CSF受容体の細胞内領域を中心にPCR-SSCP法にて構造異常をスクリーニングした。3例において膜貫通部を含む領域に構造異常が強く疑われた。G-CSF受容体の構造異常が骨髄性白血病の病態にも関与している可能性があり、現在、塩基配列を解析中である。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] Takenaka K.: "Generation of human natural killer cells from peripheral blood CD34+ cells mobilized by granulocyte colony-stimulating factor" Br.J.Haematol.92(4). 788-794 (1996)
[Publications] Miyamoto T.: "Persistence of multipotent progenitors expressing AML1/ETO transcripts in long-term remission patients with t(8;21)acute myelogenous leukemia" Blood. 87(11). 4789-4796 (1996)
[Publications] Kuroiwa M.: "Effects of granulocyte colony-stimulating factor on the hemostatic system in healthy volunteers" Int.J.Hematol.63(4). 311-316 (1996)
[Publications] Kanaji T.: "A sequence analysis of von Willebrand factor mRNA,gene,and pseudogene in two patients with von Willebrand disease type 2B,and an investigation of gene conversion in its gene" Int.J.Hematol.64(1). 53-59 (1996)
[Publications] Izuhara K.: "Signal transduction pathway of interleukin-4 and interleukin-13 in human B cells derived from X-linked severe combined immunodeficiency patients" J.Biol.Chem.271(2). 619-622 (1996)
[Publications] Esaki T.: "Schedule-dependent reversion of acquired cisplatin resistance by 5-fluorouracil in a newly established cisplatin-resistant HST-1 human squamous carcinoma cell line" Int.J.Cancer.65(4). 479-484 (1996)
[Publications] Harada M.: "G-CSF-induced mobilization of peripheral blood stem cells from healthy adults for allogeneic transplantation" J.Hematother.5(1). 63-71 (1996)
[Publications] Kuga S.: "Suppression of superoxide anion production by interleukin-10 is accompanied by a downregulation of the genes for subunit proteins of NADPH oxidase" Exp.Hematol.24(2). 151-157 (1996)
[Publications] Miyamoto T.: "Serum concentration of the soluble interleukin-2 receptor for monitoring acute graft-versus-host disease" Bone Marrow Transplant.17(2). 185-190 (1996)
[Publications] Kimura N.: "High prevalence of T cell receptor D delta 2(D delta)J delta rearrangement in CD7-positive early T cell acute lymphoblastic leukemia" Leukemia. 10(4). 650-657 (1996)
[Publications] Tanaka,Y.: "Effect of IL-10 on collagen-induced arthritis in mice" Inflamm.Res.45. 283-288 (1996)
[Publications] Nishizaka H.: "Molecular bases for inherited human complement C6 deficiency in two unrelated individuals" J.Immunol.156(6). 2309-2315 (1996)
[Publications] Kondo S.: "Expression of CD26/dipeptidyl peptidase IV in adult T cell leukemia/lymphoma(ATLL)" Leuk.Res.20(4). 357-363 (1996)
[Publications] Harada M.: "Granulocyte colony-stimulating factor-induced mobilization of peripheral blood stem cells for autologous and allogeneic transplantation. Fukuoka Bone Marrow Transplantation Group" Cancer Chemother.Pharmacol.38 Suppl. S115-119 (1996)
[Publications] Tojo A.: "In vitro model of toxin therapy targeted against murine myeloid leukemia cells" Cancer Chemother.Pharmacol.38 Suppl. S37-39 (1996)
[Publications] Asano Y.: "Effect of(-)-epigallocatechin gallate on leukemic blast cells from patients with acute myeloblastic leukemia" Life Sciences. 60(2). 135-142 (1997)
[Publications] Asano Y.: "Analysis of G-CSF receptor in various hematological disorders.Fukuoka International Symposium on Medical Science(Niho Y.ed)" Kyushu University Press.,Fukuoka, 12(1-12) (1996)

1996 Fiscal Year Annual Research Report

サイトカインを介した造血幹細胞の増殖と分化の制御機構の解析

Principal Investigator

仁保 喜之 九州大学, 医学部, 教授 (60091287)

Research Products

[Publications] Takenaka K.: "Generation of human natural killer cells from peripheral blood CD34+ cells mobilized by granulocyte colony-stimulating factor" Br.J.Haematol.92(4). 788-794 (1996)

[Publications] Miyamoto T.: "Persistence of multipotent progenitors expressing AML1/ETO transcripts in long-term remission patients with t(8;21)acute myelogenous leukemia" Blood. 87(11). 4789-4796 (1996)

[Publications] Kuroiwa M.: "Effects of granulocyte colony-stimulating factor on the hemostatic system in healthy volunteers" Int.J.Hematol.63(4). 311-316 (1996)

[Publications] Kanaji T.: "A sequence analysis of von Willebrand factor mRNA,gene,and pseudogene in two patients with von Willebrand disease type 2B,and an investigation of gene conversion in its gene" Int.J.Hematol.64(1). 53-59 (1996)

[Publications] Izuhara K.: "Signal transduction pathway of interleukin-4 and interleukin-13 in human B cells derived from X-linked severe combined immunodeficiency patients" J.Biol.Chem.271(2). 619-622 (1996)

[Publications] Esaki T.: "Schedule-dependent reversion of acquired cisplatin resistance by 5-fluorouracil in a newly established cisplatin-resistant HST-1 human squamous carcinoma cell line" Int.J.Cancer.65(4). 479-484 (1996)

[Publications] Harada M.: "G-CSF-induced mobilization of peripheral blood stem cells from healthy adults for allogeneic transplantation" J.Hematother.5(1). 63-71 (1996)

[Publications] Kuga S.: "Suppression of superoxide anion production by interleukin-10 is accompanied by a downregulation of the genes for subunit proteins of NADPH oxidase" Exp.Hematol.24(2). 151-157 (1996)

[Publications] Miyamoto T.: "Serum concentration of the soluble interleukin-2 receptor for monitoring acute graft-versus-host disease" Bone Marrow Transplant.17(2). 185-190 (1996)

[Publications] Kimura N.: "High prevalence of T cell receptor D delta 2(D delta)J delta rearrangement in CD7-positive early T cell acute lymphoblastic leukemia" Leukemia. 10(4). 650-657 (1996)

[Publications] Tanaka,Y.: "Effect of IL-10 on collagen-induced arthritis in mice" Inflamm.Res.45. 283-288 (1996)

[Publications] Nishizaka H.: "Molecular bases for inherited human complement C6 deficiency in two unrelated individuals" J.Immunol.156(6). 2309-2315 (1996)

[Publications] Kondo S.: "Expression of CD26/dipeptidyl peptidase IV in adult T cell leukemia/lymphoma(ATLL)" Leuk.Res.20(4). 357-363 (1996)

[Publications] Harada M.: "Granulocyte colony-stimulating factor-induced mobilization of peripheral blood stem cells for autologous and allogeneic transplantation. Fukuoka Bone Marrow Transplantation Group" Cancer Chemother.Pharmacol.38 Suppl. S115-119 (1996)

[Publications] Tojo A.: "In vitro model of toxin therapy targeted against murine myeloid leukemia cells" Cancer Chemother.Pharmacol.38 Suppl. S37-39 (1996)

[Publications] Asano Y.: "Effect of(-)-epigallocatechin gallate on leukemic blast cells from patients with acute myeloblastic leukemia" Life Sciences. 60(2). 135-142 (1997)

[Publications] Asano Y.: "Analysis of G-CSF receptor in various hematological disorders.Fukuoka International Symposium on Medical Science(Niho Y.ed)" Kyushu University Press.,Fukuoka, 12(1-12) (1996)

仁保喜之九州大学, 医学部, 教授 (60091287)