• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2004 Fiscal Year Final Research Report Summary

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  The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (60313128)

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)
Project Period (FY) 2002 – 2004
Keywordsinfant leukemia / 11q23 translocation / MLL gene / ABI-1 gene / AF4q31 gene / SEPTIN6 gene / AF4 gene
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.

  • Research Products

    (24 results)

All 2004 2003 2002

All Journal Article (24 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
  • [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

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

URL: 

Published: 2006-07-11  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi