2003 Fiscal Year Annual Research Report

転座型白血病のDNAチップを用いた分子機構の解析

Research Project

Project/Area Number	15023214
Research Institution	The University of Tokyo
Principal Investigator	林泰秀東京大学, 医学部附属病院, 講師 (30238133)
Keywords	遺伝子 / ゲノム / バイオテクノロジー / マイクロアレイ / 癌
Research Abstract	転座型白血病細胞の新規転座関連遺伝子を単離して、その遺伝子の発生と分化における役割およびキメラ遺伝子の標的遺伝子を検索した。我々はこれまで11q23転座型白血病のMLL遺伝子の相手遺伝子をCBP, P300,ABI1,AF5q31など8種単離した。今年度は転座型急性リンパ性白血病(ALL)の新鮮検体を用いて、転座の相手による発現の相違をDNAChipを用いて検索した。t(4;11)15検体、t(11,19)6検体、t(5;11)2検体および対照としてt(12;21)6検体、t(1;19)3検体をAffymetrix社のDNA Chip(12,600個)により発現プロファイルの解析を行った。t(4;11)とt(11;19)の両方に共通して発現がみられる遺伝子がFLT3,HOXA9,HOXA10等50種にみられた。MLL再構成のある21検体中予後による発現パターンの相違がみられ(P=0.01)、転写因子のCBF2遺伝子が予後良好群で、CDP遺伝子が予後不良群で高発現を示した。また21例で共通して発現が高かったFLT3遺伝子の変異を調べたところ、乳児ALL 44例中8例(18%)で変異がみられた。また小児ALL 112例では、高2倍体ALL 19例中4例(21.5%)に変異がみられたが、TEL-AML1、E2A-PBX1、BCR-ABL例では変異はみられなかった。これらの遺伝子の発現を定量reverse transcriptase(RT)-PCRでチェックしたところ、ほぼアレイの発現と一致していた。これらの遺伝子を詳細に検討し、共通する下流遺伝子をしぼる作業を進めている。現在、昨年単離したMLL-SEPT6融合cDNAを導入した細胞をマウスに移植し、増殖や造腫瘍性の検討も行っている。

Research Products

(11 results)

All Other

All Publications (11 results)

[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)
[Publications] Terui, K: "Successful treatment of acute myelomonocytic leukaemia with NUP98-HOXDII fusion transcripts and monitoring of minimal residual disease."Br.J.Haematol. 120・2. 274-276 (2003)
[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)
[Publications] Taketani T: "AML1/RUNX1 mutations are infrequent, but related to AML-MO, acquired trisomy 21, and leukemic transformation in pediatric hematologic malignancies."Genes Chromosomes Cancer. 38・1. 1-7 (2003)
[Publications] Echlin-Bell DR: "Polymorphisms in the MLL breakpoint cluster region (BCR)."Hum Genet. 113・1. 80-91 (2003)
[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)
[Publications] Xu G: "Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome."Blood. 102・8. 2960-2968 (2003)
[Publications] Tsutsumi S: "Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearrangements."Cancer Res. 63・16. 4882-4887 (2003)
[Publications] Hirose Y: "Comprehensive analysis of gene alterations in acute megakaryoblastic leukemia of Down's syndrome."Leukemia. 17・11. 2250-2252 (2003)
[Publications] Obana K: "Aberrations of p16LNK4A, p14ARF and p15INK4B genes in pediatric solid tumors."Int J Oncol.. 23・4. 11511-11577 (2003)
[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)

2003 Fiscal Year Annual Research Report

転座型白血病のDNAチップを用いた分子機構の解析

Principal Investigator

林 泰秀 東京大学, 医学部附属病院, 講師 (30238133)

Research Products

[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)

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

[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)

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

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

[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)

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

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

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

[Publications] Obana K: "Aberrations of p16LNK4A, p14ARF and p15INK4B genes in pediatric solid tumors."Int J Oncol.. 23・4. 11511-11577 (2003)

[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)

林泰秀東京大学, 医学部附属病院, 講師 (30238133)