Genomewide methylation analysis of juvenile myelomonocytic leukemia

• Project/Area Number: 22790975
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Nagoya University
• Principal Investigator: MURAMATSU Hideki 名古屋大学, 医学部附属病院, 助教 (00572570)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 若年性骨髄単球性白血病 / メチル化解析 / エピジェネティック

Research Abstract

We analyzed JMML patients' genomic DNA with the methylation array for whole genome methylation analysis, and validated by pyrosequencing technique. As a result, promoters of CDKM2A, H19, CALCA, IGF2, and BMP4 are significantly highly methylated in JMML patients compared to normal control, but methylation status of those genes are not associated with clinical outcome.

Research Products

• [Journal Article] Molecular lesions in childhood and adult acute megakaryoblastic leukaemia (2012)
  • Author(s): Hama A, Muramatsu H, Makishima H, Sugimoto Y, Szpurka H, Jasek M, O' Keefe C, Takahashi Y, Sakaguchi H, Doisaki S, Shimada A, Watanabe N, Kato K, Kiyoi H, Naoe T, Kojima S, Maciejewski JP
  • Journal Title: British journal of haematology Volume: 156 Pages: 316-325
  • Peer Reviewed
• [Journal Article] Incidence, clinical features, and risk factors of idiopathic pneumonia syndrome following hematopoietic stem cell transplantation in children (2012)
  • Author(s): Sakaguchi H, Takahashi Y, Watanabe N, Doisaki S, Muramatsu H, Hama A, Shimada A, Yagasaki H, Kudo K, Kojima S
  • Journal Title: Pediatric blood & cancer Volume: 58 Pages: 780-784
  • Peer Reviewed
• [Journal Article] Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia : novel pathogenetic lesions (2012)
  • Author(s): Muramatsu H, Makishima H, Maciejewski JP
  • Journal Title: Seminars in oncology Volume: 39 Pages: 67-73
  • Peer Reviewed
• [Journal Article] Incidence, clinical features, and risk factors of idiopathic pneumonia syndrome followins hematopoietic stem cell transplantation in children (2012)
  • Author(s): Sakaguchi H, et al
  • Journal Title: Pediatric blood & cancer Volume: 58 Issue: 5 Pages: 780-784
  • DOI: 10.1002/pbc.23298
  • Peer Reviewed
• [Journal Article] Autoimmune-like hepatitis following unrelated BMT successfully treated with rituximab (2011)
  • Author(s): Narita A, et al
  • Journal Title: Bone marrow transplantation Volume: 2011(In press) Issue: 4 Pages: 600-602
  • DOI: 10.1038/bmt.2011.124
  • Year and Date: 2011-06-13
  • Peer Reviewed
• [Journal Article] Excellent outcomes of children with CML treated with imatinib mesylate compared to that in pre-imatinib era (2011)
  • Author(s): Muramatsu H, Takahashi Y, Sakaguchi H, Shimada A, Nishio N, Hama A, Doisaki S, Yagasaki H, Matsumoto K, Kato K, Kojima S
  • Journal Title: International journal of hematology Volume: 93 Pages: 186-191
  • NAID: 10029533124
  • Peer Reviewed
• [Journal Article] CD20-negative Epstein-Barr virus-associated post-transplant lymphoproliferative disease refractory to rituximab in a patient with severe aplastic anemia (2011)
  • Author(s): Muramatsu H, Takahashi Y, himoyama Y, Doisaki S, Nishio N, Ito Y, Hama A, Shimada A, Yagasaki H, Ito M, Kojima S
  • Journal Title: International journal of hematology Volume: 93 Pages: 779-781
  • NAID: 10029535631
  • Peer Reviewed
• [Journal Article] Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA-identical related donors (2011)
  • Author(s): Watanabe N, Takahashi Y, Matsumoto K, Horikoshi Y, Hama A, Muramatsu H, Yoshida N, Yagasaki H, Kudo K, Horibe K, Kato K, Kojima S
  • Journal Title: Pediatr Transplant Volume: 15 Pages: 642-649
  • Peer Reviewed
• [Journal Article] Prognostic factors for outcomes of pediatric patients with refractory or relapsed acute leukemia undergoing allogeneic progenitor cell transplantation (2011)
  • Author(s): Watanabe N, Takahashi Y, Matsumoto K, Hama A, Muramatsu H, Doisaki S, Horibe K, Kato K, Kojima S
  • Journal Title: Biol Blood Marrow Transplant Volume: 17 Pages: 516-523
  • Peer Reviewed
• [Journal Article] Autoimmune lymphoproliferative syndrome-like disease with somatic KRAS mutation (2011)
  • Author(s): Takagi M, Shinoda K, Piao J, Mitsuiki N, Matsuda K, Muramatsu H, Doisaki S, Nagasawa M, Morio T, Kasahara Y, Koike K, Kojima S, Takao A, Mizutani S
  • Journal Title: Blood Volume: 117 Pages: 2887-2890
  • Peer Reviewed
• [Journal Article] Distinct impact of imatinib on growth at prepubertal and pubertal ages of children with chronic myeloid leukemia (2011)
  • Author(s): Shima H, Tokuyama M, Tanizawa A, Tono C, Hamamoto K, Muramatsu H, Watanabe A, Hotta N, Ito M, Kurosawa H, Kato K, Tsurusawa M, Horibe K, Shimada H
  • Journal Title: J Pediatr Volume: 159 Pages: 676-681
  • Peer Reviewed
• [Journal Article] Aberrant phosphorylation of STAT5 by granulocyte-macrophage colony-stimulating factor in infant cytomegalovirus infection mimicking juvenile myelomonocytic leukemia (2011)
  • Author(s): Nishio N, Takahashi Y, Tanaka M, Xu Y, Yoshida N, Sakaguchi H, Doisaki S, Hama A, Muramatsu H, Shimada A, Kojima S
  • Journal Title: Leukemia research Volume: 35 Pages: 1261-1264
  • Peer Reviewed
• [Journal Article] Reduced-intensity conditioning for alternative donor hematopoietic stem cell transplantation in patients with dyskeratosis congenita (2011)
  • Author(s): Nishio N, Takahashi Y, Ohashi H, Doisaki S, Muramatsu H, Hama A, Shimada A, Yagasaki H, Kojima S
  • Journal Title: Pediatr Transplant Volume: 15 Pages: 161-166
  • Peer Reviewed
• [Journal Article] Autoimmune-like hepatitis following unrelated BMT successfully treated with rituximab (2011)
  • Author(s): Narita A, Muramatsu H, Takahashi Y, Sakaguchi H, Doisaki S, Nishio N, Hama A, Shimada A, Ito M, Kojima S
  • Journal Title: Bone marrow transplantation Volume: (in press)
  • Peer Reviewed
• [Journal Article] Relapse of aplastic anemia in children after immunosuppressive therapy : a report from the Japan Childhood Aplastic Anemia Study Group (2011)
  • Author(s): Kamio T, Ito E, Ohara A, Kosaka Y, Tsuchida M, Yagasaki H, Mugishima H, Yabe H, Morimoto A, Ohga S, Muramatsu H, Hama A, Kaneko T, Nagasawa M, Kikuta A, Osugi Y, Bessho F, Nakahata T, Tsukimoto I, Kojima S
  • Journal Title: Haematologica Volume: 96 Pages: 814-819
  • Peer Reviewed
• [Journal Article] Mutations profile of polycythemia vera and essential thrombocythemia among Japanese children. (2011)
  • Author(s): Ismael O, Shimada A, Hama A, Sakaguchi H, Doisaki S, Muramatsu H, Yoshida N, Ito M, Takahashi Y, Akita N, Sunami S, Ohtsuka Y, Asada Y, Fujisaki H, Kojima S
  • Journal Title: Pediatric blood & cancer Volume: (in press)
  • Peer Reviewed
• [Journal Article] Analysis of mutations and recombination activity in RAG-deficient patients (2011)
  • Author(s): Asai E, Wada T, Sakakibara Y, Toga A, Toma T, Shimizu T, Nampoothiri S, Imai K, Nonoyama S, Morio T, Muramatsu H, Kamachi Y, Ohara O, Yachie A
  • Journal Title: Clin Immunol Volume: 138 Pages: 172-177
  • NAID: 120002772030
  • Peer Reviewed
• [Journal Article] Mutations profile of polycythemia vera and essential thrombocythemia among Japanese children (2011)
  • Author(s): Ismael O, et al
  • Journal Title: Pediatric blood & cancer Volume: (In press) Issue: 3 Pages: 530-535
  • DOI: 10.1002/pbc.23409
  • Peer Reviewed
• [Journal Article] Excellent outcomes of children with CML treated with imatinib mesylate compared to that in pre-imatinib era. (2011)
  • Author(s): Muramatsu H, et al.
  • Journal Title: Int J Hematol. Volume: 93(2) Pages: 186-191
  • NAID: 10029533124
  • Peer Reviewed
• [Journal Article] Analysis of mutations and recombination activity in RAG-deficient patients. (2011)
  • Author(s): Asai E
  • Journal Title: Clin Immunol. Volume: 138 Pages: 172-177
  • Peer Reviewed
• [Journal Article] Reduced-intensity conditioning for alternative donor hematopoietic stemcell transplantation in patients with dyskeratosis congenita. (2011)
  • Author(s): Nishio N, et al.
  • Journal Title: Pediatr Transplant. Volume: 15(2) Pages: 161-166
  • Peer Reviewed
• [Journal Article] Mutations of E3 ubiquitin ligase Cbl family members but not TET2 mutations are pathogenic in Juvenile Myelomonocytic Leukemia. (2010)
  • Author(s): Muramatsu H, et al.
  • Journal Title: Blood Volume: 115 Pages: 1969-1975
  • Peer Reviewed
• [Journal Article] Outcome of 125 children with CML who received transplants from unrelated donors : the Japan Marrow Donor Program (JMDP) (2010)
  • Author(s): Muramatsu H, et al.
  • Journal Title: Biol Blood Marrow Transplant. Volume: 16 Pages: 231-238
  • Peer Reviewed
• [Journal Article] Danaparoid as the prophylaxis for hepatic veno-occlusive disease after allogeneic hematopoietic stem cell transplantation in childhood hematological malignancy. (2010)
  • Author(s): Sakaguchi H
  • Journal Title: Pediatric blood & cancer. Volume: 55 Pages: 1118-1125
  • Peer Reviewed
• [Journal Article] Spectrum of molecular defects in juvenile myelomonocytic leukaemia includes ASXL1 mutations. (2010)
  • Author(s): Sugimoto Y, et al.
  • Journal Title: Br J Haematol. Volume: 150(1) Pages: 83-87
  • Peer Reviewed
• [Journal Article] Autoimmune lymphoproliferative syndrome-like disease with somatic KRAS mutation. (2010)
  • Author(s): Takagi M, et al.
  • Journal Title: Blood Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Comparison of matched-sibling donor BMT and unrelated donor BMT in children and adolescent with acquired severe aplastic anemia. (2010)
  • Author(s): Yagasaki H, et al.
  • Journal Title: Bone Marrow Transplant. Volume: 45(10) Pages: 1508-1513
  • Peer Reviewed
• [Presentation] 若年性骨髄単球性白血病におけるDNAメチル化の臨床的意義 (2011)
  • Author(s): 坂口大俊, 他
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] NRAS体細胞モザイク変異(G12D)により若年性骨髄単球性白血病を発症した一例 (2011)
  • Author(s): 土居崎小夜子, 他
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] HLA不一致血縁ドナーからの小児造血幹細胞移植の検討:HLA一致血縁ドナーおよびHLA一致非血縁ドナーとの比較 (2011)
  • Author(s): 村松秀城, 他
  • Organizer: 第33回日本造血細胞移植学会総会
  • Place of Presentation: 松山
  • Year and Date: 2011-03-09
• [Presentation] ダウン症候群に合併した一過性骨髄異常増殖症148例の後方視的解析 (2010)
  • Author(s): 村松秀城, 他
  • Organizer: 第52回日本小児血液学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-18
• [Presentation] Low-Dose Cytosine Arabinoside Therapy for Neonates with Down Syndrome (DS) and Transient Leukemia (TL) (2010)
  • Author(s): Muramatsu H, et al.
  • Organizer: 52nd ASH annual meeting
  • Place of Presentation: 米国 オーランド
  • Year and Date: 2010-12-04
• [Presentation] Imatinib and HSCT improves the outcome of pediatric patients with PhALL (2010)
  • Author(s): 村松秀城, 他
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] 若年性骨髄単球性白血病発症の分子機構 (2010)
  • Author(s): 村松秀城, 他
  • Organizer: 第113回日本小児科学会学術集会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-04-25