2001 Fiscal Year Annual Research Report

白血病の分化誘導療法をめざしたETV6/ARG融合遺伝子の機能解析

Research Project

Project/Area Number	12671016
Research Institution	Research Institute, Internationa Medical Center of Japan
Principal Investigator	佐藤裕子国立国際医療センター, 研究所・臨床病理部・超微細構造研究所, 室長 (10137713)
Keywords	ETV6 / ARG / STI571 / チロシン・キナーゼ / チロシン燐酸化 / transformation / IL3independent / BaF3 / NIH3T3
Research Abstract	私達がt(1;12)(q25;p12)転座を持つAML-M3細胞株HT93Aより単離したETV6/ARG融合遺伝子はチロシン・キナーゼである。昨年度に引き続き、ETV6/ARG融合遺伝子の機能を解析すべく、以下のように実験を行った(要旨は米国血液学会総会で発表した。現在、論文を準備中)。 1.ETV6/ARG full constructをテトラサイクリン誘導プロモータを組込んだBa/F3細胞にtransfectした。 2.テトラサイクリン誘導をかけて、ETV6/ARGを発現させたところ、IL3independentの細胞増殖や細胞死の著明な抑制が認められた。 3.ETV6/ABLでリン酸化されることが知られているPI3K, SHC, ras-GAP, CRK-Lのシグナル伝達分子は、同様にETV6/ARGを発現したBa/F3細胞でリン酸化されていた。 4.ETV6/ARG発現細胞ではSTI571(Gleevec)投与により急速にアポトーシスに陥ることが判明した。この機構はCDK inhibitor P18/INK4Cのup-regulationによる細胞周期アレストによるものであることが証明できた。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Iijima Y, Sato Y, et al.: "Transformation of BaF3 cells and Rat-1 cells by ETV6/ARG."Oncogene. (in press).
[Publications] Sato Y, Rowley JD, et al.: "A New recurrent translocation t(1;3)(p36;p21)associated with therapy-relatedleukemia"Genes Chromosom Cancer. (in press).
[Publications] Izumi H, Sato Y, et al.: "High telomerase activity correlates with the. stabilities of genome and DNA ploidy renal cell carcinoma"Neoplasia. (in press).
[Publications] Nishimura N, Sato Y, et al.: "Suppression of Arg kinase by STI571 induces cell cycle arrest through induction of CDK inhibitor p18/INK4c."Blood. 98. 102a (2001)
[Publications] Okuda K, Sato Y, et al.: "The TEL/ARG leikemia oncogene promotes viability and hyperresponsiveness to hematopoietic growth factors"Blood. 98. 802a (2001)
[Publications] Kogure K, Sato Y, et al.: "Targetedintegration of foreign DNA into a defined locus on chromosome 19 in K562 cells usingΛΛ-derived components hematopoietic cell using AAV-derived components"Int J Hematol. 73. 469-475 (2001)
[Publications] Sato Y, Rowlcy JD et al.: "Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones"Leukemia. 5. 1193-1202 (2001)
[Publications] Ogiue-Ikeda M, Sato Y, et al.: "Inhibition of leukemia cell growth under magnetic fields of up to 8T."IEEE Transactions on Magnetics. 37. 2912-2914 (2001)
[Publications] Kano Y, Sato M, et al.: "In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination commonly used with antileukemic agents"Blood. 1999-2007 (2001)
[Publications] Nakazato H, Sato Y, et al.: "TEL/MNI fusion in a AML-M2 patient who showed strong resistance to treatment"Brit Haematol. 113. 1080-1082 (2001)
[Publications] Nishino M, Sato Y, et al.: "Stem cell factor prevents Fas-mediated apoptosis of human erythroid precursor cells with Src-familly kinase dependency"Exp Hematol. 29. 19-29 (2001)

2001 Fiscal Year Annual Research Report

白血病の分化誘導療法をめざしたETV6/ARG融合遺伝子の機能解析

Principal Investigator

佐藤 裕子 国立国際医療センター, 研究所・臨床病理部・超微細構造研究所, 室長 (10137713)

Research Products

[Publications] Iijima Y, Sato Y, et al.: "Transformation of BaF3 cells and Rat-1 cells by ETV6/ARG."Oncogene. (in press).

[Publications] Sato Y, Rowley JD, et al.: "A New recurrent translocation t(1;3)(p36;p21)associated with therapy-relatedleukemia"Genes Chromosom Cancer. (in press).

[Publications] Izumi H, Sato Y, et al.: "High telomerase activity correlates with the. stabilities of genome and DNA ploidy renal cell carcinoma"Neoplasia. (in press).

[Publications] Nishimura N, Sato Y, et al.: "Suppression of Arg kinase by STI571 induces cell cycle arrest through induction of CDK inhibitor p18/INK4c."Blood. 98. 102a (2001)

[Publications] Okuda K, Sato Y, et al.: "The TEL/ARG leikemia oncogene promotes viability and hyperresponsiveness to hematopoietic growth factors"Blood. 98. 802a (2001)

[Publications] Kogure K, Sato Y, et al.: "Targetedintegration of foreign DNA into a defined locus on chromosome 19 in K562 cells usingΛΛ-derived components hematopoietic cell using AAV-derived components"Int J Hematol. 73. 469-475 (2001)

[Publications] Sato Y, Rowlcy JD et al.: "Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones"Leukemia. 5. 1193-1202 (2001)

[Publications] Ogiue-Ikeda M, Sato Y, et al.: "Inhibition of leukemia cell growth under magnetic fields of up to 8T."IEEE Transactions on Magnetics. 37. 2912-2914 (2001)

[Publications] Kano Y, Sato M, et al.: "In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination commonly used with antileukemic agents"Blood. 1999-2007 (2001)

[Publications] Nakazato H, Sato Y, et al.: "TEL/MNI fusion in a AML-M2 patient who showed strong resistance to treatment"Brit Haematol. 113. 1080-1082 (2001)

[Publications] Nishino M, Sato Y, et al.: "Stem cell factor prevents Fas-mediated apoptosis of human erythroid precursor cells with Src-familly kinase dependency"Exp Hematol. 29. 19-29 (2001)

佐藤裕子国立国際医療センター, 研究所・臨床病理部・超微細構造研究所, 室長 (10137713)