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2009 Fiscal Year Final Research Report

Analysis of regulatory mechanism of hematopoiesis and exploration of the pathogenesis of hematopoietic neoplasms through comprehensive genetic analysis

Research Project

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Project/Area Number 17013022
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

OGAWA Seishi  The University of Tokyo, 医学部附属病院, 特任准教授 (60292900)

Project Period (FY) 2008 – 2009
Research Abstract

Hematopoietic neoplasms are caused by deregulation of normal components of the hematopoietic system by gene mutations. In fact, many of genetic changes identified as a cause of hematopoietic neoplasms involves those genes implicated in normal regulation of hematopoiesis. In this study, we performed comprehensive genetic analyses of more than 2,000 hematopoietic neoplasms using high-density SNP arrays. We identified a number of genetic alterations involved in the pathogenesis of hematopoietic neoplasms, including gain-of-function mutations of c-CBL in myeloid neoplasms and inactivation mutations of A20 in B-lineage lymphomas, followed by their functional analysis. These findings are thought to contribute not only to our understanding of molecular pathogenesis of hematopoietic cancers, but also to adding our knowledge on regulatory mechanisms of normal hematopoiesis, together with the development of novel diagnostics and therapeutics for these neoplasms.

  • Research Products

    (50 results)

All 2010 2009 2008 Other

All Journal Article (49 results) Remarks (1 results)

  • [Journal Article] Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms.2010

    • Author(s)
      Thoennissen NH, Krug UO, Lee DH, Kawamata N, Iwanski GB, Lasho T, Weiss T, Nowak D, Koren-Michowitz M, Kato M, Sanada M, Shih LY, Nagler A, Raynaud SD, Muller-Tidow C, Mesa R, Haferlach T, Gillil, DG, Tefferi A, Ogawa S, Koeffler HP.
    • Journal Title

      Blood.

  • [Journal Article] SNP array analysis of tyrosine kinase inhibitor-resistant chronic myeloid leukemia identifies heterogeneous secondary genomic alterations.2010

    • Author(s)
      Nowak D, Ogawa S, Muschen M, Kato M, Kawamata N, Meixel A, Nowak V, Kim HS, Kang S, Paquette R, Chang MS, Thoenissen NH, Mossner M, Hofmann WK, Kohlmann A, Weiss T, Haferlach T, Haferlach C, Koeffler HP.
    • Journal Title

      Blood. 115

      Pages: 1049-1053

  • [Journal Article] Hes1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogenous leukemia.2010

    • Author(s)
      Nakahara F, Sakata-Yanagimoto M, Komeno Y, Kato N, Uchida T, Haraguchi K, Kumano K, Harada Y, Harada H, Kitaura J, Ogawa S, Kurokawa M, Kitamura T, Chiba S.
    • Journal Title

      Blood.

  • [Journal Article] Derivation of functional mature neutrophils from human embryonic stem cells.2009

    • Author(s)
      Yokoyama Y, Suzuki T, Sakata-Yanagimoto M, Kumano K, Higashi K, Takato T, Kurokawa M, Ogawa S, Chiba S.
    • Journal Title

      Blood. 113

      Pages: 6584-6592

  • [Journal Article] High-resolution genomic copy number profiling of glioblastoma multiforme by single nucleotide polymorphism DNA microarray.2009

    • Author(s)
      Yin D, Ogawa S, Kawamata N, Tunici P, Finocchiaro G, Eoli M, Ruckert C, Huynh T, Liu G, Kato M, Sanada M, Jauch A, Dugas M, Black KL, Koeffler HP.
    • Journal Title

      Mol Cancer Res. 7

      Pages: 665-677

  • [Journal Article] Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms.2009

    • Author(s)
      Sanada M, Suzuki T, Shih LY, Otsu M, Kato M, Yamazaki S, Tamura A, Honda H, Sakata-Yanagimoto M, Kumano K, Oda H, Yamagata T, Takita J, Gotoh N, Nakazaki K, Kawamata N, Onodera M, Nobuyoshi M, Hayashi Y, Harada H, Kurokawa M, Chiba S, Mori H, Ozawa K, Omine M, Hirai H, Nakauchi H, Koeffler HP, Ogawa S
    • Journal Title

      Nature. 460

      Pages: 904-908

  • [Journal Article] Molecular allelokaryotyping of T-cell prolymphocytic leukemia cells with high density single nucleotide polymorphism arrays identifies novel common genomic lesions and acquired uniparental disomy.2009

    • Author(s)
      Nowak D, Le Toriellec E, Stern MH, Kawamata N, Akagi T, Dyer MJ, Hofmann WK, Ogawa S, Koeffler HP.
    • Journal Title

      Haematologica. 94

      Pages: 518-527

  • [Journal Article] Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma.2009

    • Author(s)
      Lee SY, Kumano K, Nakazaki K, Sanada M, Matsumoto A, Yamamoto G, Nannya Y, Suzuki R, Ota S, Ota Y, Izutsu K, Sakata-Yanagimoto M, Hangaishi A, Yagita H, Fukayama M, Seto M, Kurokawa M, Ogawa S, Chiba S.
    • Journal Title

      Cancer Sci. 100

      Pages: 920-926

  • [Journal Article] HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism.2009

    • Author(s)
      Kawase T, Matsuo K, Kashiwase K, Inoko H, Saji H, Ogawa S, Kato S, Sasazuki T, Kodera Y, Morishima Y.
    • Journal Title

      Blood. 113

      Pages: 2851-2858

  • [Journal Article] Double minute chromosomes containing MYB gene and NUP214-ABL1 fusion gene in T-cell leukemia detected by single nucleotide polymorphism DNA microarray and fluorescence in situ hybridization.2009

    • Author(s)
      Kawamata N, Zhang L, Ogawa S, Nannya Y, Dashti A, Lu D, Lim S, Schreck R, Koeffler HP.
    • Journal Title

      Leuk Res. 33

      Pages: 569-571

  • [Journal Article] Molecular allelokaryotyping of relapsed pediatric acute lymphoblastic leukemia.2009

    • Author(s)
      Kawamata N, Ogawa S, Seeger K, Kirschner-Schwabe R, Huynh T, Chen J, Megrabian N, Harbott J, Zimmermann M, Henze G, Schrappe M, Bartram CR, Koeffler HP.
    • Journal Title

      Int J Oncol. 34

      Pages: 1603-1612

  • [Journal Article] Identified hidden genomic changes in mantle cell lymphoma using high-resolution single nucleotide polymorphism genomic array.2009

    • Author(s)
      Kawamata N, Ogawa S, Gueller S, Ross SH, Huynh T, Chen J, Chang A, Nabavi-Nouis S, Megrabian N, Siebert R, Martinez-Climent JA, Koeffler HP.
    • Journal Title

      Exp Hematol. 37

      Pages: 937-946

  • [Journal Article] Hepatoblastoma in a patient with sotos syndrome.2009

    • Author(s)
      Kato M, Takita J, Takahashi K, Mimaki M, Chen Y, Koh K, Ida K, Oka A, Mizuguchi M, Ogawa S, Igarashi T.
    • Journal Title

      J Pediatr. 155

      Pages: 937-939

  • [Journal Article] Frequent inactivation of A20 in B-cell lymphomas.2009

    • Author(s)
      Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, Niwa A, Chen Y, Nakazaki K, Nomoto J, Asakura Y, Muto S, Tamura A, Iio M, Akatsuka Y, Hayashi Y, Mori H, Igarashi T, Kurokawa M, Chiba S, Mori S, Ishikawa Y, Okamoto K, Tobinai K, Nakagama H, Nakahata T, Yoshino T, Kobayashi Y, Ogawa S.
    • Journal Title

      Nature. 459

      Pages: 712-716

  • [Journal Article] HapMap scanning of novel human minor histocompatibility antigens.2009

    • Author(s)
      Kamei M, Nannya Y, Torikai H, Kawase T, Taura K, Inamoto Y, Takahashi T, Yazaki M, Morishima S, Tsujimura K, Miyamura K, Ito T, Togari H, Riddell SR, Kodera Y, Morishima Y, Kuzushima K, Ogawa S, Akatsuka Y.
    • Journal Title

      Blood. 113

      Pages: 5041-5048

  • [Journal Article] Notch activation induces the generation of functional NK cells from human cord blood CD34-positive cells devoid of IL-15.2009

    • Author(s)
      Haraguchi K, Suzuki T, Koyama N, Kumano K, Nakahara F, Matsumoto A, Yokoyama Y, Sakata-Yanagimoto M, Masuda S, Takahashi T, Kamijo A, Takahashi K, Takanashi M, Okuyama Y, Yasutomo K, Sakano S, Yagita H, Kurokawa M, Ogawa S, Chiba S.
    • Journal Title

      J Immunol. 182

      Pages: 6168-6178

  • [Journal Article] Single nucleotide polymorphism genomic arrays analysis of t(8;21) acute myeloid leukemia cells.2009

    • Author(s)
      Akagi T, Shih LY, Ogawa S, Gerss J, Moore SR, Schreck R, Kawamata N, Liang DC, Sanada M, Nannya Y, Deneberg S, Zachariadis V, Nordgren A, Song JH, Dugas M, Lehmann S, Koeffler HP.
    • Journal Title

      Haematologica. 94

      Pages: 1301-1306

  • [Journal Article] Hidden abnormalities and novel classification of t(15;17) acute promyelocytic leukemia (APL) based on genomic alterations.2009

    • Author(s)
      Akagi T, Shih LY, Kato M, Kawamata N, Yamamoto G, Sanada M, Okamoto R, Miller CW, Liang DC, Ogawa S, Koeffler HP.
    • Journal Title

      Blood. 113

      Pages: 1741-1748

  • [Journal Article] Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype.2009

    • Author(s)
      Akagi T, Ogawa S, Dugas M, Kawamata N, Yamamoto G, Nannya Y, Sanada M, Miller CW, Yung A, Schnittger S, Haferlach T, Haferlach C, Koeffler HP.
    • Journal Title

      Haematologica. 94

      Pages: 213-223

  • [Journal Article] Chromosomal abnormalities and novel disease-related regions in progression from Barrett's esophagus to esophageal adenocarcinoma.2009

    • Author(s)
      Akagi T, Ito T, Kato M, Jin Z, Cheng Y, Kan T, Yamamoto G, Olaru A, Kawamata N, Boult J, Soukiasian HJ, Miller CW, Ogawa S, Meltzer SJ, Koeffler HP.
    • Journal Title

      Int J Cancer. 125

      Pages: 2349-2359

  • [Journal Article]2008

    • Author(s)
      Yabe T, Matsuo K, Hirayasu K, Kashiwase K, Kawamura-Ishii S, Tanaka H, Ogawa A, Takanashi M, Satake M, Nakajima K, Tokunaga K, Inoko H, Saji H, Ogawa S, Juji T, Sasazuki T, Kodera Y, Morishima Y.
    • Journal Title

      Biol Blood Marrow Transplant. 14

      Pages: 75-87

  • [Journal Article] Genome-wide loss of heterozygosity and uniparental disomy in BRCA1/2-associated ovarian carcinomas.2008

    • Author(s)
      Walsh CS, Ogawa S, Scoles DR, Miller CW, Kawamata N, Narod SA, Koeffler HP, Karlan BY.
    • Journal Title

      Clin Cancer Res. 14

      Pages: 7645-7651

  • [Journal Article] ERCC5 is a novel biomarker of ovarian cancer prognosis.2008

    • Author(s)
      Walsh CS, Ogawa S, Karahashi H, Scoles DR, Pavelka JC, Tran H, Miller CW, Kawamata N, Ginther C, Dering J, Sanada M, Nannya Y, Slamon DJ, Koeffler HP, Karlan BY.
    • Journal Title

      J Clin Oncol. 26

      Pages: 2952-2958

  • [Journal Article] Gain of GRHL2 is associated with early recurrence of hepatocellular carcinoma.2008

    • Author(s)
      Tanaka Y, Kanai F, Tada M, Tateishi R, Sanada M, Nannya Y, Ohta M, Asaoka Y, Seto M, Shiina S, Yoshida H, Kawabe T, Yokosuka O, Ogawa S, Omata M.
    • Journal Title

      J Hepatol. 49

      Pages: 746-757

  • [Journal Article] AML1-Evi-1 specifically transforms hematopoietic stem cells through fusion of the entire Evi-1 sequence to AML1.2008

    • Author(s)
      Takeshita M, Ichikawa M, Nitta E, Goyama S, Asai T, Ogawa S, Chiba S, Kurokawa M.
    • Journal Title

      Leukemia.

  • [Journal Article] Whole-genome profiling of chromosomal aberrations in hepatoblastoma using high-density single-nucleotide polymorphism genotyping microarrays.2008

    • Author(s)
      Suzuki M, Kato M, Yuyan C, Takita J, Sanada M, Nannya Y, Yamamoto G, Takahashi A, Ikeda H, Kuwano H, Ogawa S, Hayashi Y.
    • Journal Title

      Cancer Sci. 99

      Pages: 564-570

  • [Journal Article] Coordinated regulation of transcription factors through Notch2 is an important mediator of mast cell fate.2008

    • Author(s)
      Sakata-Yanagimoto M, Nakagami-Yamaguchi E, Saito T, Kumano K, Yasutomo K, Ogawa S, Kurokawa M, Chiba S.
    • Journal Title

      Proc Natl Acad Sci U S A. 105

      Pages: 7839-7844

  • [Journal Article] Exploration of the genetic basis of GVHD by genetic association studies.2008

    • Author(s)
      Ogawa S, Matsubara A, Onizuka M, Kashiwase K, Sanada M, Kato M, Nannya Y, Akatsuka Y, Satake M, Takita J, Chiba S, Saji H, Maruya E, Inoko H, Morishima Y, Kodera Y, Takehiko S.
    • Journal Title

      Biol Blood Marrow Transplant. 15

      Pages: 39-41

  • [Journal Article] Integrated analysis of copy number alterations and loss of heterozygosity in human pancreatic cancer using a high-resolution, single nucleotide polymorphism array.2008

    • Author(s)
      Lin LJ, Asaoka Y, Tada M, Sanada M, Nannya Y, Tanaka Y, Tateishi K, Ohta M, Seto M, Sasahira N, Kawabe T, Zheng CQ, Kanai F, Ogawa S, Omata M.
    • Journal Title

      Oncology. 75

      Pages: 102-112

  • [Journal Article] Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia.2008

    • Author(s)
      Lehmann S, Ogawa S, Raynaud SD, Sanada M, Nannya Y, Ticchioni M, Bastard C, Kawamata N, Koeffler HP.
    • Journal Title

      Cancer. 112

      Pages: 1296-1305

  • [Journal Article] Both Notch1 and Notch2 contribute to the regulation of melanocyte homeostasis.2008

    • Author(s)
      Kumano K, Masuda S, Sata M, Saito T, Lee SY, Sakata-Yanagimoto M, Tomita T, Iwatsubo T, Natsugari H, Kurokawa M, Ogawa S, Chiba S.
    • Journal Title

      Pigment Cell Research.

  • [Journal Article] Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA.2008

    • Author(s)
      Kawase T, Nannya Y, Torikai H, Yamamoto G, Onizuka M, Morishima S, Tsujimura K, Miyamura K, Kodera Y, Morishima Y, Takahashi T, Kuzushima K, Ogawa S, Akatsuka Y.
    • Journal Title

      Blood. 111

      Pages: 3286-3294

  • [Journal Article] Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray.2008

    • Author(s)
      Kawamata N, Ogawa S, Zimmermann M, Niebuhr B, Stocking C, Sanada M, Hemminki K, Yamatomo G, Nannya Y, Koehler R, Flohr T, Miller CW, Harbott J, Ludwig WD, Stanulla M, Schrappe M, Bartram CR, Koeffler HP.
    • Journal Title

      Proc Natl Acad Sci U S A. 105

      Pages: 11921-11926

  • [Journal Article] Molecular allelokaryotyping of pediatric acute lymphoblastic leukemias by high-resolution single nucleotide polymorphism oligonucleotide genomic microarray.2008

    • Author(s)
      Kawamata N, Ogawa S, Zimmermann M, Kato M, Sanada M, Hemminki K, Yamatomo G, Nannya Y, Koehler R, Flohr T, Miller CW, Harbott J, Ludwig WD, Stanulla M, Schrappe M, Bartram CR, Koeffler HP.
    • Journal Title

      Blood. 111

      Pages: 776-784

  • [Journal Article] Genetic profiling of myeloproliferative disorders by single-nucleotide polymorphism oligonucleotide microarray.2008

    • Author(s)
      Kawamata N, Ogawa S, Yamamoto G, Lehmann S, Levine RL, Pikman Y, Nannya Y, Sanada M, Miller CW, Gillil, DG, Koeffler HP.
    • Journal Title

      Exp Hematol. 36

      Pages: 1471-1479

  • [Journal Article] Chronic phase of ETV6-ABL1 positive CML responds to imatinib.2008

    • Author(s)
      Kawamata N, Dashti A, Lu D, Miller B, Koeffler HP, Schreck R, Moore S, Ogawa S.
    • Journal Title

      Genes Chromosomes Cancer. 47

      Pages: 919-921

  • [Journal Article] HapMap scanning of novel human minor histocompatibility antigens.2008

    • Author(s)
      Kamei M, Nannya Y, Torikai H, Kawase T, Taura K, Inamoto Y, Takahashi T, Yazaki M, Morishima S, Tsujimura K, Miyamura K, Ito T, Togari H, Riddell SR, Kodera Y, Morisima Y, Kuzushima K, Ogawa S, Akatsuka Y.
    • Journal Title

      Blood.

  • [Journal Article] AML1/Runx1 Negatively Regulates Quiescent Hematopoietic Stem Cells in Adult Hematopoiesis.2008

    • Author(s)
      Ichikawa M, Goyama S, Asai T, Kawazu M, Nakagawa M, Takeshita M, Chiba S, Ogawa S, Kurokawa M.
    • Journal Title

      J Immunol. 180

      Pages: 4402-4408

  • [Journal Article] Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells.2008

    • Author(s)
      Goyama S, Yamamoto G, Shimabe M, Sato T, Ichikawa M, Ogawa S, Chiba S, Kurokawa M.
    • Journal Title

      Cell Stem Cell. 3

      Pages: 207-220

  • [Journal Article] Oncogenic mutations of ALK kinase in neuroblastoma.2008

    • Author(s)
      Chen Y, Takita J, Choi YL, Kato M, Ohira M, Sanada M, Wang L, Soda M, Kikuchi A, Igarashi T, Nakagawara A, Hayashi Y, Mano H, Ogawa S.
    • Journal Title

      Nature. 455

      Pages: 971-974

  • [Journal Article] Therapy of relapsed leukemia after allogeneic hematopoietic cell transplant with T cells specific for minor histocompatibility antigens.

    • Author(s)
      Warren EH, Fujii N, Akatsuka Y, Chaney CN, Mito JK, Loeb KR, Gooley TA, Brown ML, Koo KK, Rosinski KV, Ogawa S, Matsubara A, Appelbaum FR, Riddell SR.
    • Journal Title

      Blood. (in press)

  • [Journal Article] Relapse of leukemia with loss of mismatched HLA due to uniparental disomy following haploidentical hematopoietic stem cell transplantation.

    • Author(s)
      Villalobos I, Takahashi Y, Akatsuka Y, Muramatsu H, Nishio N, Hama A, Yagasaki H, Saji H, Kato M, Ogawa S, Kojima S.
    • Journal Title

      Blood. (in press)

  • [Journal Article] Prognostic significance of genetic alterations detected by high-density single nucleotide polymorphism array in gastric cancer.

    • Author(s)
      Tada M, Kanai F, Tanaka Y, Sanada M, Nannya Y, Tateishi K, Ohta M, Asaoka Y, Seto M, Imazeki F, Yoshida H, Ogawa S, Yokosuka O, Omata M.
    • Journal Title

      Cancer Sci. (in press)

  • [Journal Article] CBL mutations in juvenile myelomonocytic leukemia, but not in pediatric myelodysplastic syndrome.

    • Author(s)
      Shiba N, Kato M, Myoung-ja P, Sanada M, Ito E, Fukushima K, Sako M, Arakawa H, Ogawa S, Hayashi Y.
    • Journal Title

      Leukemia. (in press)

  • [Journal Article] Genomic profiling of adult acute lymphoblastic leukemia (ALL) by single nucleotide polymorphism oligonucleotide microarray and comparison to pediatric ALL.

    • Author(s)
      Okamoto R, Ogawa S, Nowak D, Kawamata N, Akagi T, Kato K, Sanada M, Weiss T, Haferlach C, Dugas M, Ruckert C, Haferlach T, Koeffler H.
    • Journal Title

      Haematologica. (in press)

  • [Journal Article] Deregulated intracellular signaling by mutated c-CBL in myeloid neoplasms.

    • Author(s)
      Ogawa S, Shih L, Suzuki T, Otsu M, Nakauchi H, Koeffler H, Sanada M.
    • Journal Title

      Clinical Cancer Research. (in press)

  • [Journal Article] Gain-of-function c-CBL mutations associated with uniparental disomy of 11q in myeloid neoplasms.

    • Author(s)
      Ogawa S, Sanada M, Shih LY, Suzuki T, Otsu M, Nakauchi H, Koeffler HP.
    • Journal Title

      Cell Cycle. (in press)

  • [Journal Article] Impact of highly conserved HLA haplotype on acute graft-versus-host disease.

    • Author(s)
      Morishima S, Ogawa S, Matsubara A, Kawase T, Nannya Y, Kashiwase K, Satake M, Saji H, Inoko H, Kato S, Kodera Y, Sasazuki T, Morishima Y.
    • Journal Title

      Blood. (in press)

  • [Journal Article] Gastric Cancer Cell Line Hs746T Harbors a Splice Site Mutation of c-Met Causing Juxtamembrane Domain Deletion.

    • Author(s)
      Asaoka Y, Toda M, Ikenoue T, Seto M, Imai M, Miyabayashi K, Yamamoto K, Yamamoto S, Kudo Y, Mohri D, Isomura Y, Ijichi H, Tateishi K, Kanai F, Ogawa S, Omata M, Koike K.
    • Journal Title

      Biochem Biophys Res Commun. (in press)

  • [Remarks]

    • URL

      http://www.genome.umin.jp/

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Published: 2011-06-18   Modified: 2016-04-21  

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