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Cloning of responsible genes causing myelodysplasia in myelodysplastic syndrome

Research Project

Project/Area Number 09671144
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionResearch Institute, International Medical Center of Japan

Principal Investigator

SATO Yuko  Division of Molecular Cytohgenetics, Department of Clinical Pathology, 臨床病理部・超微細構造研究室, 室長 (10137713)

Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsmyelodysplastic syndrome / translocation t(1 ; 3)(p36 ; q21) / FISH / BAC library / 1p36 breakpoint / gene cloning / Molecular cytogenetics / PRDM16 / DNAファイバーFISH法 / BACライブラリー / 転座切断点 / FISH
Research Abstract

Using FISH with 13 cosmid probes (tel--FB12-CA5-G7-FD2- CB1 -ED8-FD9-G32-AE3-G50-AD8-GG4-PEBP2_C--cen), we have determined the 1p36 breakpoint of t(1 ; 3)(p36 ; q21) translocation in four myelodysplastic syndrome (MDS) patients and one adult-type CML patient : the breakpoint was between CA5 and G7 (1p36.3) in four MDS patients and between GG4-PEBP2αC (1p36.1) in the CML patient. This indicated that the 1p36 breakpoint was different between different disorders. As a next step, we made a contig map between CA5 and G7 using a total of 33 BAC clones. The breakpoints of three MDS patients were found in PAC163G9 clone, and that of the remaining MDS patient was found in BAC737N8, suggesting that the 1p36 breakpoint in MDS may be scattered in 340 kb region at most, since BAC clone generally cover ca 170kb. Now, we are searching all the genes contained in the two clones through DNA sequencing to find out the responsible gene for MDS.
On the other hand, Mochizuki, et al. reported that they found out responsible genes for t(1 ; 3)(p36 ; q21) translocation (Mochizuki N, et al : A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS/EVI1 gene and is transcriptionally activated in t(1 ; 3)(p36 ; q21)-positive leukemia cells. Blood 96 : 3209, 2000) : MEL1 gene located adjacent to the 1p36 breakpoint was transcriptionally activated by the promoter of Evi1 gene located adjacent to the 3q21 breakpoint only in t(1 ; 3)(p36 ; q21)-positive leukemia cells. We also studied whether the MEL1 gene was expressed in two MDS patients of our series. We found that PRDM16 gene, not MEL1, which shows highly homology to MEL1 with only difference in 3' end was highly expressed although this gene was not expressed in any other cell lines (in preparation).

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Iijima Y,Sato Y, et al.: "A new partner gene of the ETV6/TEL, ARG (ABL related gene, or ABL2) cloned in a AML-M3 cell line with t(1;12)(q25;p13)."Blood. 95. 2126-2131 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Eguchi M, Sato Y, et al.: "Fusion of the ETV6 to neutrophin-3 receptor TrkC in acute myeloid leukemia with t(12;15)(p13;q25). Blood 93:1355-1363,1999."Blood. 93. 1355-1363 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suto Y,Sato Y, et al.: "TEL is fused to a previously unknown gene, STL,in a t(6;12)(q23;p13) translocation in a patient with acute lymphoblastic leukemia."Genes Chromosom Cancer. 18. 254-268 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato Y, et al.: "Indentification of pericentric inversion 12, inv(12)(p13.1q11) by fluorescence in situ hybridization in a patient with acute myeloid leukemia (AML-M6)."Cancer Genet Cytogenet. 97. 157-160 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato Y, et al.: "Heterogeneity in the breakpoints in balanced rearrangements involving band 12p13 in hematologic malignancies identified by FISH : TEL (ETV6) is involved in only one-half."Blood. 97. 4886-4893 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 佐藤裕子: "転座型白血病の遺伝子診断"現代診療. 31. 95-106 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 佐藤裕子: "血液病の染色体検査〜自動化の試み、FISH法なども含めて"日常診療と血液. 8. 297-304 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 佐藤裕子: "in situ hybridization:微小染色体構造解析への応用"臨床検査. 42. 1017-1022 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 佐藤裕子: "Fluorescence in situ hybridization(FISH)法による遺伝子マッピングとゲノム異常の解析"Diabetes Frontier. 9. 327-332 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 佐藤裕子: "染色体-その分析と臨床応用"細胞. 42. 423-424 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 佐藤裕子: "染色体異常の新しい解析"血液・免疫・腫瘍. 3. 873-882 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 佐藤裕子: "ETV6(TEL)遺伝子とヒト白血病"最新医学. 52. 414-426 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 園山政行,佐藤裕子: "染色体検査の理解にむけて【1】-細胞培養から染色体標本スライドの作成まで-"Modern Media. 43. 82-91 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 園山政行,佐藤裕子: "染色体検査の理解にむけて【2】-染色体分染法(1)-"Modern Media. 43. 217-227 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 園山政行,佐藤裕子: "染色体検査の理解にむけて【3】-染色体分染法(2)-"Modern Media. 43. 396-404 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato Y, Rowley JD: "Chromosomal abnormalities in childhood malignant diseases, In Hematology of infancy and childhood. Nathan DG, Orkin SH (eds)"W.B.Saunders Company, Philadelphia. 1147-1182 1914 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 佐藤裕子: "「造血器腫瘍と染色体異常」造血幹細胞-分子から臨床まで-三浦恭定編集"南江堂、東京. 134-142 272 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iijima Y, Ito T, Oikawa T, Eguchi M, Eguchi-Ishimae M, Kamada N, Kishi K, Asano S, Sakaki Y, Sao Y: "A new ETV6 (TEL) partner gene, ARG (ABL related gene or ABL2) identified in a AML-M3 cell line with the t(1 ; 12)(q25 ; p13) translocation."Blood. 95. 2126-2131 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Eguchi M, Eguchi-Ishimae M, Tojo A, Suzuki K, Morishita K, Sato Y, Kudo S, Tanaka K, Nagamura F, Asano S, Kamada N: "Fusion of the ETV6 to neutrophin-3 receptor TrkC in acute myeloid leukemia with t(12 ; 15)(p13 ; q25)."Blood. 93. 1355-1363 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suto Y, Sato Y, Smith SD, Rowley JD, Bohlander SK: "TEL is fused to a previously unknown gene, STL, in a t(6 ; 12)(q23 ; p13)translocation in a patient with acute lymphoblastic leukemia."Genes Chromosom Cancer. 18. 254-268 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato Y, Bohlander SK, Kobayashi H, Suto Y, Davis EM, Le Beau MM, Le Beau MM, Rowley JD: "Identification of pericentric inversion 12, inv (12)(p13.1q11) by fluorescence in situ hybridization in a patient with acute myeloid leukemia (AML-M6)."Cancer Genet Cytogenet. 97. 157-160 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato Y, Bohlander SK, Kobayashi H, Reshmi S, Suto Y, Davis EM, Espinosa III R, Hoopes R, Montgomery KT, Kucherlapati RS, Le Beau MM, Rowley JD: "Heterogeneity in the breakpoints in balanced rearrangements involving band 12p13 in hematologic malignancies identified by FISH : TEL (ETV6) is involved in only one-half."Blood. 90. 4886-4893 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato Y, Rowley JD: "Chromosomal abnormalities in childhood malignant diseases. In Hematology of infancy and childhood. Nathan DG, Orkin SH (eds), W.B.Saunders Company."Philadelphia. 1147-1182 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iijima Y, Sato Y, et al.: "A new partner gene of the ETV6/TEL, ARG(ABL related gene, or ABL2)cloned in a AML-M3 cell line with t(1;12)(q25,p13)"Blood. 95. 2126-2131 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Eguchi M, Sato Y, et al.: "Fusion of the ETV6 to neutrophin-3 receptor TrkC in acute myeloid leukemia with t(12;15)(p13:q25). Blood 93:1355-1363.1999"Blood. 93. 1355-1363 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takami Y, Sato Y, et al.: "Identification of a novel partner gene of CAN from the K562 cell line"Blood. 94(supp1). 186 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐藤裕子: "転座型白血病の遺伝子診断"現代診療. 31. 95-106 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kogure K, Sato Y, et al.: "Site-specific integration of integration of a foreign gene to AAVS1 locus on chromosonle 19 chromosome 19 in hematopoietic cell using AAV-derived component"Blood. 92. 378b (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐藤裕子: "血液病の染色体検査〜自動化の試み、FISH法なども含めて"日常診療と血液. 8. 297-304 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐藤裕子: "in situ hybridization:微小染色体構造解析への応用"臨床検査. 42. 1017-1022 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐藤裕子: "染色体-その分析と臨床応用"細胞. 42. 423-424 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐藤裕子: "染色体異常の新しい解析"血液・免疫・腫瘍. 3. 873-882 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐藤裕子: "Fluorescence in situ hybridization (FISH)法による遺伝子マッピシグとゲノム異常の解析"Diabetes Frontier. 9. 327-332 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐藤裕子: "「造血器腫瘍と染色体異常」造血幹細胞-分子から臨床まで-三浦恭定編集"南江堂、東京. 134-142/272 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sato Y, Rowley JD: "Chromosomal abnormalities in childhood malignant diseases.In Hematology of infancy and childhood.Nathan DG, Orkin SH(eds)"W.B. Saunders Company, Philadelphia. 1147-1182/1914 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Eguchi M,Sato Y,et al.: "Fusion of the ETV6 to neutrophin-3 receptor TrkC in acute myeloid leukemia with t(12;15)(p13;q25).Blood 93:1355-1363,1999." Blood. 93. 1355-1363 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iijima Y,Sato Y,et al.: "A new partner gene of the ETV6/TEL,ARG(ABL related gene,or ABL2)colned in a AML-M3 cell line with t(1;12)(q25;p13)." Blood. 92. 592a (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kogure K,Sato Y,et al.: "Site-specific integration of integration of a foreign gene to AAVSI locus on chromosome 19 chromosome 19 in hematopoietic cell using AAV-derived component." Blood. 92. 378b (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐藤裕子: "血液病の染色体検査〜自動化の試み、FISH法なども含めて" 日常診療と血液. 8. 297-304 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐藤裕子: "Fluorescence in situ hybridization(FISH)法による遺伝子マッピングとゲノム異常の解析" Diabetes Fronticr. 9. 327-332 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐藤裕子: "in situ hybridization:微小染色体構造解析への応用" 臨床検査. 42. 1017-1022 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐藤裕子: "染色体-その分析と臨床応用" 細胞. 42. 423-424 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐藤裕子: "染色体異常の新しい解析" 血液・免疫・腫瘍. 3. 873-882 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐藤裕子: "転座型白血病の遺伝子診断" 現代診療. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐藤裕子: "「造血器腫瘍と染色体異常」造血幹細胞-分子から臨床まで-三浦恭定編集" 南江堂、東京, 134-142(272) (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suto Y,et al.: "TEL is fused to a previously unknown gene,STL,in at (6;12) (q23;p13) translocation in a patient with acute lymphoblastic leukemia." Genes Chromosom Cancer. 18. 254-268 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato Y,et al.: "Identification of pericentric inversion 12,inv(12) (p13.1q11) by fluorescence in situ hybridization in a patient with acute myeloid leukemia (AML-M6)." Cancer Genet Cytogenet. 97. 157-160 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato Y,et al.: "Heterogeneity in the breakpoints in balanced rearrangements involving band 12p13 in hematologic malignancies identified by FISH : TEL (ETV6) is involved in only one-half." Blood. 97. 4886-4893 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 佐藤裕子: "ETV6(TEL)遺伝子とヒト白血病" 最新医学. 52. 414-426 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato Y,Rowley JD: "Chromosomal abnormalities in childhood malignant diseases. In Hematology of infancy and childhood. Nathan DG,Orkin SH (eds)" W.B.Saunders Company,Philadelphia, 1147-1182 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 佐藤裕子: "「造血器腫瘍と染色体異常」造血幹細胞-分子から臨床まで- 三浦恭定編集" 南江堂、東京, 134-142 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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