Molecular/cellular biological analysis of pathogenesis and spontaneous remission mechanism in Down syndrome transient myeloproliferative disorder

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591552
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tokyo Dental College
• Principal Investigator: MIYAUCHI Jun 東京歯科大学, 歯学部, 教授 (20146707)
• Co-Investigator(Kenkyū-buntansha): KAWAGUCHI Hiroyuki 防衛医科大学校, 小児科, 講師 (00313130)
• Project Period (FY): 2011 – 2013
• Keywords: 一過性骨髄増殖症 / ダウン症候群 / 造血微小環境 / 造血因子 / 胎児造血 / 胎児肝間質細胞 / 自然治癒

Research Abstract

In neonates with Down syndrome, hematological abnormalities similar to acute myeloid leukemia may be seen but usually spontaneously disappear. This disorder, called transient myeloproliferative disorder (TMD), is thought to be a unique myeloid neoplasm arising in the fetal liver. The mechanism of its spontaneous remission is unclear. In this study, using cell culture techniques, we demonstrated that stromal cells constituting microenvironment of the fetal liver support the growth of TMD blasts and that one of the hematopoietic growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF), produced by the stromal cells play an important role. These results indicate that fetal hematopoietic microenvironment is involved in the onset, progression and spontaneous remission of TMD.

Research Products

• [Journal Article] Fetal liver stromal cells support blast growth in transient abnormal myelopoiesis in Down syndrome through GM-CSF (2014)
  • Author(s): Miyauchi J, Kawaguchi H
  • Journal Title: Journal of Cellular Biochemistry Volume: 115 Pages: 1176-1186
  • DOI: 10.1002/jcb.24764
  • Peer Reviewed
• [Journal Article] Bilateral intralobar sequestration of the lung with a bridging isthmus : pathologic and radiologic findings (2014)
  • Author(s): Fukuzawa R, Komori K, Kohno T, Hirose S, Miyauchi J
  • Journal Title: Pediatric Developmental Pathology Volume: 17 Pages: 55-58
  • DOI: 10.2350/13-08-1371-CR.1
  • Peer Reviewed
• [Journal Article] ダウン症候群関連骨髄増殖性疾患:自然経過と造血微小環境の役割 (2014)
  • Author(s): 宮内潤
  • Journal Title: 東京女子医科大学雑誌 Volume: 8(Extra 2) Pages: E257-267
  • Peer Reviewed
• [Journal Article] リンパ腫の病期診断と骨髄浸潤 (2014)
  • Author(s): 宮内潤、松本公宏
  • Journal Title: 日本臨床「リンパ腫:検査・診断と治療の最新動向」 Volume: 72 Pages: 456-461
• [Journal Article] Collision lymph node metastasis of rectal and prostate adenocarcinomas (2013)
  • Author(s): Miyauchi J, Asahara F, Matsui J
  • Journal Title: Pathology International Volume: 63 Pages: 425-427
  • DOI: 10.1111/pin.12084
  • Peer Reviewed
• [Journal Article] Autoimmunity and persistent RAS-mutated clones long after the spontaneous regression of JMML (2013)
  • Author(s): Takagi M, Piao J, Kawaguchi H, Imai C, Ogawa A, Watanabe A, Akiyama K, Kobayashi C, Mori M, Ko K, Mizutani S
  • Journal Title: Leukemia Volume: 27 Pages: 1926-1928
  • DOI: 10.1038/leu.2013.82
  • Peer Reviewed
• [Journal Article] Targeted inactivation of nuclear interaction partner of ALK (NIPA) disrupts meiotic prophase (2013)
  • Author(s): Illert AL, Kawaguchi H, Antinozzi C, Bassermann F, de Fend LQ, von Klitzing C, Hiwatari M, Peschel C, de Rooij DG, Morris SW, Barchi M, Duyster J
  • Journal Title: Development Volume: 139 Pages: 2523-2534
  • DOI: 10.1242/dev.073072
  • Peer Reviewed
• [Journal Article] 肝臓の乳児性血管内皮腫の1例 (2013)
  • Author(s): 宮内潤、赤塚誠也
  • Journal Title: 日本小児血液・がん学会誌 Volume: 50 Pages: 155
• [Journal Article] Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia (2012)
  • Author(s): Doisaki S, Muramatsu H, Shimada A, Takahashi Y, Esaki M, Sato M, Kawaguchi H, Kinoshita A, Sotomatsu M, Hayashi Y, Furukawa-Hibi Y, Yamada K, Hoshino H, Kiyoi H, Yoshida N, Sakaguchi H, Narita A, Wang X, Ismael O, Xu Y, Nishio N, Tanaka M, Hama A, Koike K, Kojima S
  • Journal Title: Blood Volume: 120 Pages: 1485-1488
  • DOI: 10.1182/blood-2012-02-406090
  • Peer Reviewed
• [Journal Article] 小児のMDS:その特徴と診断上の注意点 (2012)
  • Author(s): 川口裕之、宮内潤
  • Journal Title: 病理と臨床 Volume: 30 Pages: 848-855
• [Journal Article] 乳腺葉状腫瘍の1女児例 (2012)
  • Author(s): 宮内潤、赤塚誠也
  • Journal Title: 小児血液・がん学会誌 Volume: 49 Pages: 184
• [Journal Article] Expression of megakaryocytic and myeloid markers in blasts of transient abnormal myelopoiesis in a stillbirth with Down syndrome : report of histopathological findings of an autopsy case (2011)
  • Author(s): Ishigaki H, Miyauchi J, Yokoe A, Nakayama M, Yanagi T, Taga T, Ohta S, Itoh Y, Ogasawara K
  • Journal Title: Human Pathology Volume: 42 Pages: 141-145
  • DOI: 10.1016/j.humpathol.2010.06.012
  • Peer Reviewed
• [Journal Article] 急性リンパ性白血病地固め療法中に肺病変より脊椎硬膜外膿瘍を発症した接合菌症 (2011)
  • Author(s): 露無圭子、中谷綾、宮内潤、岡本真一郎
  • Journal Title: 臨床血液 Volume: 52 Pages: 718-721
  • Peer Reviewed
• [Presentation] 複数の腫瘤性髄外病変を認めた急性巨核芽球性白血病の1歳女児例 (2014)
  • Author(s): 野村智章、川口裕之、中村麻里、横山光紀、山本かずな、濱本学、草野智佳子、中川紀子、川村陽一、野々山恵章
  • Organizer: 第117回日本小児科学会
  • Place of Presentation: 名古屋市
  • Year and Date: 20140411-13
• [Presentation] 髄液細胞中に反応性T細胞の増多をきたし、治療中の中枢神経再発を疑われた標準リスクB前駆細胞型ALLの一例 (2013)
  • Author(s): 磯部清孝、川口裕之、野々山恵章
  • Organizer: 第55回日本小児血液・がん学会
  • Place of Presentation: 福岡市
  • Year and Date: 2013-11-30
• [Presentation] The role of fetal hematopoietic micro- environment in the growth of blast progenitors in transient abnormal myelopoiesis in Down syndrome (2013)
  • Author(s): Miyauchi J, Kawaguchi H
  • Organizer: 第55回日本小児血液・がん学会学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2013-11-29
• [Presentation] ダウン症児の一過性骨髄造血異常症(TAM)における芽球の増殖は胎児間質細胞が産生するGM-CSFに依存する (2013)
  • Author(s): 宮内潤
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌市
  • Year and Date: 2013-06-08
• [Presentation] 直腸癌と前立腺癌のリンパ節転移衝突癌の2例 (2012)
  • Author(s): 宮内潤、浅原史卓、松井淳一、赤塚誠也、馬場秀雄
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-26
• [Presentation] A case of splenectomy to stage IV splenic DLBCL with PET-positive residual disease before auto PBSCT (2011)
  • Author(s): Okada S, Watanabe T, Hirose T, Miura K, Katoh M, Yamafuji K, Akatsuka S, Miyauchi J, Mori S, Kikuchi M, Kanda Y
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 20111014-16
• [Presentation] 若年性骨髄単球性白血病の発症機序に関する最近の知見(コンパニオンミーティング10:骨髄のトピックス) (2011)
  • Author(s): 宮内潤
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 20110428-30
• [Presentation] TAM芽球の増殖・分化に及ぼす造血因子と造血微小環境の影響.厚生労働省科学研究費補助金:「ダウン症候群でみられる一過性骨髄異常増殖症の重症度分類のための診断基準と治療指針の作成に関する研究」(研究代表者:林泰秀) (2011)
  • Author(s): 宮内潤
  • Organizer: 平成23年度第1回班会議
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-11-04
• [Book] 「近医にて赤血球増加の指摘」p.37-44、「健診にて白血球増多の指摘」p.165-171、北川昌伸・定平吉都・伊藤雅文(編):「見逃してはならない血液疾患(病理からみた44症例) (2014)
  • Author(s): 宮内潤(分担執筆)
  • Total Pages: 278
  • Publisher: 医学書院(東京)
• [Book] 中枢神経系腫瘍.日本病理学会小児腫瘍組織分類委員会(編)、小児腫瘍組織カラーアトラス(第6巻) (2013)
  • Author(s): 藤本純一郎、浜崎豊、平戸純子、北條洋、堀江弘、井上健、石田剛、宮内潤、森川征彦、中川温子、中山雅弘、小田義直、大喜多肇、横山繁昭
  • Total Pages: 125
  • Publisher: 金原出版(東京)
• [Book] 「小児の骨髄と白血病の特徴」p.45-49、「BCR-ABL1陽性慢性骨髄性白血病」p.52-57、「Down症候群関連骨髄増殖性疾患」p.180-184、「巨核球の形態異常をきたす骨髄性腫瘍の鑑別」p.208-213、定平吉都・北川昌伸(編):造血器腫瘍(腫瘍病理鑑別診断アトラス) (2013)
  • Author(s): 宮内潤(分担執筆)
  • Total Pages: 290
  • Publisher: 文光堂(東京)
• [Book] 「急性好塩基球性白血病」p.228-231、「形質細胞白血病」p.232-235、「若年性骨髄単球性白血病」p.284-288、別冊日本臨床:新領域別症候群シリーズNo.23「血液症候群(第2版)III」 (2013)
  • Author(s): 宮内潤(分担執筆)
  • Total Pages: 767
  • Publisher: 日本臨床社(東京)
• [Book] Unique myeloid leukemias in young children with Down syndrome : Cell origin, association with hematopoietic microenvironment and leukemo- genesis. in :"Prenatal Diagnosis and Screening for Down Syndrome"(edited by Subarata Dey) (2011)
  • Author(s): Miyauchi J
  • Total Pages: 107-128(232)
  • Publisher: InTech Open Access Publisher (Rijeka, Croatia)