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Molecular and epidemiologic analysis of the development of infant leukemia

Research Project

Project/Area Number 14370242
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionThe University of Tokyo

Principal Investigator

IDA Kohmei (2003-2004)  The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (60313128)

林 泰秀 (2002)  東京大学, 医学部附属病院, 講師 (30238133)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Miyuki  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (60205391)
KOH Katsuyoshi  The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (50359618)
HAYASHI Yasuhide  Gunma Prefectural Institute of Public Health and Environmental Sciences, Researcher, 技師 (30238133)
井田 孔明  東京大学, 医学部附属病院, 助手 (60313128)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordsinfant leukemia / 11q23 translocation / MLL gene / ABI-1 gene / AF4q31 gene / SEPTIN6 gene / AF4 gene / 遺伝子 / ゲノム / バイオテクノロジー / マイクロアレイ / 白血病 / MLL / 癌
Research Abstract

11q23 translocations involving MLL gene are recurrent translocations in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). As a partner gene of MLL, we have cloned SEPT6, LCX, LAF4 genes in t(X;11), t(10;11), t(2;11), respectively in pediatric ALL and AML. Expression of approximately 2.3-, 3.1-, and 4.6-kb SEPT6 transcripts was simultaneously detected in fetal lung, liver, and brain, in all of the adult tissues except brain, and in ALL and AML cell lines. However, the expression of an approximately 2.7-kb transcript was detected alone in fetal heart and adult brain. The MLL-SEPT6 fusion gene was analyzed in vitro and in vivo. As a partner gene of NUP98, we have cloned HDXC11, HOXD11, HOXA13 genes in t(11;12), t(2;11), t(7;11), respectively in pediatric AML.
Using oligonucleotide microarray analysis, we identified distinct expression profiles for 23 ALL samples with 11q23 translocations, including t(4;11) (n=15), t(11;19) (N=6), and t(5;11) (n=2), compared with 9 ALL samples with other translocations, including t(12;21) (n=6) and t(1;19) (n=3). Gene expression scores of FLT3, Meis1, and CD44 for samples with MLL rearrangements were particularly high compared with those for other ALL samples. Statistical analysis of the gene expression profiles for the 21 ALL samples with MLL rearrangements at diagnosis revealed two subgroups that exclusively correlated with prognosis but not with any other clinico-pathological factor. The transcription factors CBF2 and CDP were highly expressed in the poor and good prognosis subgroups, respectively. In addition, their downstream target genes were differentially expressed. These findings provide new insights into the biological mechanisms of leukemogenesis and prognosis for pediatric ALL with MLL rearrangements.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (47 results)

All 2004 2003 2002 Other

All Journal Article (30 results) Publications (17 results)

  • [Journal Article] Infant acute lymphoblastic leukemia with MLL gene rearrangements : outcome following intensive chemotherapy and hematopoietic stem cell transplantation.2004

    • Author(s)
      Kosaka Y
    • Journal Title

      Blood 104

      Pages: 3527-3534

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Fetal origin of the GATA1 mutation in identical twins with transient myeloproliferative disorder and acute megakaryoblastic leukemia accompanying Down syndrome.2004

    • Author(s)
      Shimada A
    • Journal Title

      Blood 103

      Pages: 366-366

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant acute lymphoblastic leukemia (ALL) with MLL rearrangement and pediatric ALL with hyperdiploidy.2004

    • Author(s)
      Taketani T
    • Journal Title

      Blood 103

      Pages: 1085-1088

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Infant acute lymphoblastic leukemia with MLL gene rearrangements : outcome following intensive chemotherapy and hematopoietic stem cell transplantation.2004

    • Author(s)
      Kosaka Y, Koh K, Kinukawa N, Wakazono Y, Isoyama K, Oda T, Hayashi Y, Ohta S, Moritake H, Oda M, Nagatoshi Y, Kigasawa H, Ishida Y, Ohara A, Hanada R, Sako M, Sato T, Mizutani S, Horibe K, Ishii E.
    • Journal Title

      Blood 104

      Pages: 3527-3534

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Fetal origin of the GATA1 mutation in identical twins with transient myeloproliferative disorder and acute megakaryoblastic leukemia accompanying Down syndrome.2004

    • Author(s)
      Shimada A, Xu G, Toki T, Kimura H, Hayashi Y, Ito E.
    • Journal Title

      Blood 103

      Pages: 366-366

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant acute lymphoblastic leukemia (ALL) with MLL rearrangement and pediatric ALL with hyperdiploidy.2004

    • Author(s)
      Taketani T, Taki T, Sugita K, Furuichi Y, Ishii E, Hanada R, Tsuchida M, Sugita K, Ida K, Hayashi Y.
    • Journal Title

      Blood 103

      Pages: 1085-1088

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] FLT3 mutations in the activation loop of tyrosine kinase domain are Frequently found in infant acute lymphoblastic leukemia(ALL) with MLL rearrangement and pediatric ALL with hyperdiploidy.2004

    • Author(s)
      Taketani T
    • Journal Title

      Blood 103・3

      Pages: 1085-1088

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Fetal origin of the GATA1 mutation in identical twins with transient myeloproliferative disorder and acute megakaryoblastic leukemia accompanying Down syndrome.2004

    • Author(s)
      Shimada A
    • Journal Title

      Blood 103・1

      Pages: 366-366

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Proinflammatory cytokinemia associated with transient myeloproliferative disorder in down syndrome.2004

    • Author(s)
      Shimada A
    • Journal Title

      Biol Neonate. 85・3

      Pages: 167-172

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization of genomic breakpoints in MLL and CBP in leukemia patients witht(11;16).2004

    • Author(s)
      Zhang Y
    • Journal Title

      Genes Chromosomes Cancer. 41・3

      Pages: 257-265

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma.2004

    • Author(s)
      Takita J
    • Journal Title

      Genes Chromosomes Cancer. 40・2

      Pages: 120-132

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Infant acute lymphoblastic leukemia with MLL gene rearrangements : outcome following intensive chemotherapy and hematopoietic stem cell transplantation.2004

    • Author(s)
      Kosaka Y
    • Journal Title

      Blood 104・12

      Pages: 3527-3534

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Fusion of an AF4-related gene, LAF4,to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).2003

    • Author(s)
      Hiwatari M
    • Journal Title

      Oncogene. 22

      Pages: 2851-2855

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] AML1/RUNX1 mutations are infrequent, but related to AML-MO, acquired trisomy 21,and leukemic transformation in pediatric hematologic malignancies.2003

    • Author(s)
      Taketani T
    • Journal Title

      Genes Chromosomes Cancer. 38

      Pages: 1-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearrangements.2003

    • Author(s)
      Tsutsumi S
    • Journal Title

      Cancer Res. 63

      Pages: 4882-4887

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down's syndrome.2003

    • Author(s)
      Xu G
    • Journal Title

      Blood. 102

      Pages: 2960-2968

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).2003

    • Author(s)
      Hiwatari M, Taki T, Taketani T, Taniwaki M, Sugita K, Okuya M, Eguchi M, Ida K, Hayashi Y.
    • Journal Title

      Oncogene. 22

      Pages: 2851-2855

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] AML1/RUNX1 mutations are infrequent, but related to AML-M0, acquired trisomy 21, and leukemic transformation in pediatric hematologic malignancies.2003

    • Author(s)
      Taketani T, Taki T, Takita J, Tsuchida M, Hanada R, Hongo T, Kaneko T, Manabe A, Ida K, Hayashi Y.
    • Journal Title

      Genes Chromosomes Cancer. 38

      Pages: 1-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearrangements.2003

    • Author(s)
      Tsutsumi S, Taketani T, Nishimura K, Ge X, Taki T, Sugita K, Ishii E, Hanada R, Ohki M, Aburatani H, Hayashi Y.
    • Journal Title

      Cancer Res. 63

      Pages: 4882-4887

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down's syndrome.2003

    • Author(s)
      Xu G, Nagano M, Kanezaki R, Toki T, Hayashi Y, Taketani T, Taki T, Mitui T, Koike K, Kato K, Imaizumi M, Sekine I, Ikeda Y, Hanada R, Sako M, Kudo K, Kojima S, Ohneda O, Yamamoto M, Ito E.
    • Journal Title

      Blood. 102

      Pages: 2960-2968

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The chromosome translocation t(7;11)(p15;p15) in acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13,but not HOXA9.2002

    • Author(s)
      Taketani T
    • Journal Title

      Genes Chromosomes Cancer 34

      Pages: 437-443

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with the t(2;11)(q31;p15).2002

    • Author(s)
      Taketani T
    • Journal Title

      Cancer Res. 62

      Pages: 33-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel NUP98-HOXC11 Fusion Gene Resulted from a Chromosomal Break within Exon 1 of HOXC11 in Acute Myeloid Leukemia with t(11;12)(p15;q13).2002

    • Author(s)
      Taketani T
    • Journal Title

      Cancer Res. 62

      Pages: 4571-4574

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] SEPTIN6,a Human Homologue to Mouse Septin6, Is Fused to MLL in Infant Acute Myeloid Leukemia with Complex Chromosomal Abnormalities Involving 11q23 and Xq242002

    • Author(s)
      Ono R
    • Journal Title

      Cancer Res. 62

      Pages: 333-337

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23).2002

    • Author(s)
      Ono R
    • Journal Title

      Cancer Res. 62

      Pages: 4075-4080

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The chromosome translocation t(7;11)(p15;p15) in acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13, but not HOXA9.2002

    • Author(s)
      Taketani T, Taki T, Ono R, Kobayashi Y, Ida K, Hayashi Y.
    • Journal Title

      Genes Chromosomes Cancer 34

      Pages: 437-443

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with the t(2;11)(q31;p15).2002

    • Author(s)
      Taketani T, Taki T, Shibuya N, Ito E, Kitazawa J, Terui K, Hayashi Y.
    • Journal Title

      Cancer Res. 62

      Pages: 33-37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel NUP98-HOXC11 Fusion Gene Resulted from a Chromosomal Break within Exon 1 of HOXC11 in Acute Myeloid Leukemia with t(11;12)(p15;q13).2002

    • Author(s)
      Taketani T, Taki T, Shibuya N, Kikuchi A, Hanada R, Hayashi Y.
    • Journal Title

      Cancer Res. 62

      Pages: 4571-4574

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] SEPTIN6, a Human Homologue to Mouse Septin6, Is Fused to MLL in Infant Acute Myeloid Leukemia with Complex Chromosomal Abnormalities Involving 11q23 and Xq24.2002

    • Author(s)
      Ono R, Taki T, Taketani T, Kawaguchi H, Taniwaki M, Okamura T, Kawa K, Hanada R, Kobayashi M, Hayashi Y.
    • Journal Title

      Cancer Res. 62

      Pages: 333-337

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23).2002

    • Author(s)
      Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y.
    • Journal Title

      Cancer Res. 62

      Pages: 4075-4080

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Xinh PT: "The breakpoints at 1p36.3 detected with BAC/PAC probes in three MDS/AML(M4) patients with t(1;3)(p36;q21) translocation : in the first intron and in the 5' region of MEL1."Genes Chromosome Cancerr. 36・3. 313-317 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Terui, K: "Successful treatment of acute myelomonocytic leukaemia with NUP98-HOXD11 fusion transcripts and monitoring of minimal residual disease."Br.J.Haematol. 120・2. 274-276 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiwatari M: "Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23)."Oncogene. 22・18. 2851-2855 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Taketani T: "AML1/RUNX1 mutations are infrequent, but related to AML-M0, acquired trisomy 21, and leukemic transformation in pediatric hematologic malignancies"Genes Chromosomes Cancer. 38・1. 1-7 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Echlin-Bell DR: "Polymorphisms in the MLL breakpoint cluster region (BCR)."Hum Genet. 113・1. 80-91 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chen YY: "Genomic structure and mutational analysis of the human KIF1Balpha gene located at 1p36.2 in neuroblastoma."Int J Oncol. 23・3. 737-744 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Xu G: "Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome."Blood. 102・8. 2960-2968 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsutsumi S: "Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearrangements."Cancer Res. 63・16. 4882-4887 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirose Y: "Comprehensive analysis of gene alterations in acute megakaryoblastic leukemia of Down's syndrome."Leukemia. 17・11. 2250-2252 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Obana K: "Aberrations of p16INK4A, p14ARF and p15INK4B genes in pediatric solid tumors."Int J Oncol.. 23・4. 11511-11577 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Taketani T: "FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant acute lymphoblastic leukemia (ALL) with MLL rearrangement and pediatric ALL with hyperdiploidy."Blood. 103・3. 1085-1088 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Taketani T: "The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with the t(2;11)(q31;p15)"Cancer Res. 62. 33-37 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ono R: "SEPTIN6, a Human Homologue to Mouse Sptin6, Is Fused to MLL in Infant Acute Myeloid Leukemia with Complex Chromosomal Abnormalities Involving 11q23 and Xq24"Cancer Res. 62. 333-337 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Taketani T: "The t(7;11)(p15;p15) in acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13, but not HOXA9"Genes Chromosomes Cancer 34:33-41, 2002. 34. 437-443 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ono R: "LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23)"Cancer Res. 62. 4075-4080 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Taketani T: "Novel NUP98-HOXC11 Fusion Gene Resulted from a Chromosomal Break within Exon 1 of HOXC11 in Acute Myeloid Leukemia with t(11;12)(p15;q13)"Cancer Res. 62. 4571-4574 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitagawa Y: "Prevalent involvement of illegitimate V(D)J recombination in chromosome 9p21 deletions in Lymphoid Leukemia"J Biol Chem. 227. 46289-46297 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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