Clinical and biological significance of granulocyte colony stimulating factor receptor gene abnormalities those found in severe congenital neutropenia

• Project/Area Number: 20591243
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Yamagata University
• Principal Investigator: MITSUI Tetsuo (MTSUI Tetsuo) 山形大学, 医学部, 講師 (30270846)
• Co-Investigator(Kenkyū-buntansha): KAWAKAMI Takako 山形大学, 医学部, 助教 (90312743) ; HAYASAKA Kiyoshi 山形大学, 医学部, 教授 (20142961)
• Project Period (FY): 2008 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: CSF3R / 先天性好中球減少症 / 白血病化 / ゲノム不安定性 / G-CSF受容体 / 切断型遺伝子異常 / CSF3受容体 / Shwachman-Diamond症候群 / 受容体切断型遺伝子異常 / 生天性好中球減少症

Research Abstract

We conducted sequential G-CSF receptor (CSF3) gene analysis of patients with severe congenital neutropenia, and found a heterogeneous mutation (c. 1947C>T : Ala569Val) in the receptor gene that coded right above cell membrane. This mutation is confirmed as the acquired gene mutation. The patient did not show any change in her clinical course and this mutation disappeared from her marrow six months later. Genome instability like this is interesting in relation to leukemic change of severe congenital neutropenia.

Research Products

• [Journal Article] Treatment with lactose (galactose)-restricted and medium-chain triglyceride-supplemented formula for neonatal intrahepatic cholestasis caused by citrin deficiency (2012)
  • Author(s): Hayasaka K, et al
  • Journal Title: J Inher Meta Dis Volume: 2 Pages: 37-44
  • DOI: 10.1007/8904_2011_42
  • ISBN: 9783642247576, 9783642247583
  • Peer Reviewed
• [Journal Article] Congenital dysplastic microcephaly and hypoplasia of the brainstem and cerebellum with diffuse intracranial calcification (2012)
  • Author(s): Nakamura K, Hayasaka K, et al
  • Journal Title: J Child Neurol Volume: 27 Issue: 2 Pages: 218-221
  • DOI: 10.1177/0883073811416239
  • Peer Reviewed
• [Journal Article] 当院においてRosen T20プロトコールで治療した若年骨肉腫12例 (2011)
  • Author(s): 川上貴子, 簡野美弥子, 高橋憲幸, 目黒亨, 仙道大, 三井哲夫, 樋口智佳子, 土屋登嗣, 勝浦理彦, 清水行敏, 小山内俊久, 早坂清
  • Journal Title: 小児がん Volume: 48 Pages: 276-283
  • Peer Reviewed
• [Journal Article] Paternal mosaicism of an STXBP1 mutation in OS (2011)
  • Author(s): Saitu H, Hayasaka K, et al
  • Journal Title: Clin Genet Volume: 80 Issue: 5 Pages: 484
  • DOI: 10.1111/j.1399-0004.2010.01575.x
  • Peer Reviewed
• [Journal Article] Molecular diagnosis and clinical onset of Charcot-Marie-Tooth disease in Japan (2011)
  • Author(s): Abe A, Hayasaka K, et al
  • Journal Title: J Hum Genet Volume: 56 Issue: 5 Pages: 364-368
  • DOI: 10.1038/jhg.2011.20
  • NAID: 10030659221
  • Peer Reviewed
• [Journal Article] 基礎疾患を有する者に対するワクチン接種 (2011)
  • Author(s): 要藤裕孝, 三井哲夫, 佐藤晶論, 西村直子, 一見良司, 田邊卓也
  • Journal Title: 小児科臨床 Volume: 64 Pages: 508-510
• [Journal Article] 当院においてRosen T20プロトコール変法で化療した若年骨肉腫12例 (2011)
  • Author(s): 川上貴子, ら
  • Journal Title: 小児がん Volume: 48 Pages: 276-283
  • NAID: 110009857581
  • Peer Reviewed
• [Journal Article] Molecular diagnosis and clinical onset of Charcot-Marie-Tooth diseases in Japan (2011)
  • Author(s): Abe A, et al
  • Journal Title: J Hum Genet Volume: 56 Pages: 364-364
  • Peer Reviewed
• [Journal Article] 再発・難治性非ホジキンリンパ腫の治療 (2010)
  • Author(s): 三井哲夫
  • Journal Title: 日小血会誌 Volume: 24 Pages: 250-254
  • NAID: 10026624752
• [Journal Article] Retrospective analysis of non-anaplastic peripheral T-cell lymphoma in pediatric patients in Japan (2010)
  • Author(s): Kobayashi R, Mitsui T, 他12名
  • Journal Title: Pediatr Blood Cancer Volume: 54 Issue: 2 Pages: 212-5
  • DOI: 10.1002/pbc.22329
  • Peer Reviewed
• [Journal Article] Polyalanine expansion of PHOX2B in congenital central hypoventilation syndrome : rs17884724 : A>C is associated with seven-alanine expansion (2010)
  • Author(s): Arai H, Hayasaka K, 他5名
  • Journal Title: J Hum Genet Volume: 55 Issue: 1 Pages: 4-7
  • DOI: 10.1038/jhg.2009.109
  • Peer Reviewed
• [Journal Article] Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome (2010)
  • Author(s): Numakura C, Hayasaka K, 他5名
  • Journal Title: Am J Med Genet Volume: 152A Issue: 9 Pages: 2355-2359
  • DOI: 10.1002/ajmg.a.33556
  • Peer Reviewed
• [Journal Article] Frameshift mutations of the ARX gene in familial Ohtahara syndrome (2010)
  • Author(s): Kato M, Hayasaka K, 他3名
  • Journal Title: Epilepsia Volume: 51 Issue: 9 Pages: 1679-84
  • DOI: 10.1111/j.1528-1167.2010.02559.x
  • Peer Reviewed
• [Journal Article] Phenotypic variability in a family with Townes-Brocks syndrome (2010)
  • Author(s): Sudo Y, Hayasaka K, 他4名
  • Journal Title: J Hum Genet Volume: 55 Issue: 8 Pages: 550-551
  • DOI: 10.1038/jhg.2010.64
  • NAID: 10030736454
  • Peer Reviewed
• [Journal Article] Non-obese early onset diabetes mellitus in mutant cryptochrome 1 transgenic mice (2010)
  • Author(s): Okano S, Hayasaka K, 他4名
  • Journal Title: Eur J Clin Invest Volume: 40 Issue: 11 Pages: 1011-1017
  • DOI: 10.1111/j.1365-2362.2010.02359.x
  • Peer Reviewed
• [Journal Article] Compound heterozygous PMP22 deletion mutations causing severe Charcot-Marie-Tooth disease type 1. (2010)
  • Author(s): Abe A, Hayasaka K, 他7人
  • Journal Title: J Hum Genet Volume: 55 Issue: 11 Pages: 771-773
  • DOI: 10.1038/jhg.2010.106
  • NAID: 10030737757
  • Peer Reviewed
• [Journal Article] STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern (2010)
  • Author(s): Saitsu H, Hayasaka K, 他20人
  • Journal Title: Epilepsia Volume: 51 Issue: 12 Pages: 2397
  • DOI: 10.1111/j.1528-1167.2010.02728.x
  • Peer Reviewed
• [Journal Article] 再発・難治性非ホジキンリンパ腫の治療 (2010)
  • Author(s): 三井哲夫
  • Journal Title: 日小血会誌 24 Pages: 250-254
  • NAID: 10026624752
• [Journal Article] Retrospective Analysis of Non-Anaplastic Peripheral T-Cell Lymphoma in Pediatric Patients in Japan. (2010)
  • Author(s): Kobayashi R, Mitsui T, et al.
  • Journal Title: Pediatr Blood Cancer 54 Pages: 212-215
  • Peer Reviewed
• [Journal Article] 再発・難治性非ホジキンリンパ腫の治療 (2010)
  • Author(s): 三井哲夫
  • Journal Title: 日本小児血液学会雑誌 Volume: 24 Pages: 250-254
  • NAID: 10026624752
• [Journal Article] Retrospective Analysis of Non-Anaplastic Peripheral T-Cell Lymphoma in Pediatric Patients in Japan (2010)
  • Author(s): Kobayashi R, Mitsui T, et al.
  • Journal Title: Pediatr Blood Cancer Volume: 54 Pages: 212-215
  • Peer Reviewed
• [Journal Article] Severe hemorrhagic colitis caused by dasatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia (2009)
  • Author(s): Shimokaze T, Mitsui T, Takeda H, Kawakami T, Arai T, Ito M, Iwaba A, Izumino H, Takahashi N, Kanno M, Sendo D, Hayasaka K.
  • Journal Title: Pediatr Hematol Oncol Volume: 26 Pages: 448-53
  • Peer Reviewed
• [Journal Article] Lymphoma Committee, Japanese Pediatric Leukemia/Lymphoma Study Group : Retrospective analysis of relapsed or primary refractory childhood lymphoblastic lymphoma in Japan (2009)
  • Author(s): Mitsui T, Mori T, Fujita N, Inada H, Horibe K, Tsurusawa M
  • Journal Title: Pediatr Blood Cancer Volume: 52 Issue: 5 Pages: 591-595
  • DOI: 10.1002/pbc.21941
  • Peer Reviewed
• [Journal Article] Severe hemorrhagic colitis caused by dasatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia. (2009)
  • Author(s): Shimokaze T, Mitsui T, et al.
  • Journal Title: Pediat Hematol Oncol 26 Pages: 448-453
  • Peer Reviewed
• [Journal Article] Lymphoma Committee, Japanese Pediatric Leukemia/Lymphoma Study Group.Retrospective analysis of relapsed or primary refractory childhood lymphoblastic lymphoma in Japan. (2009)
  • Author(s): Mitsui T, Mori T, et al.
  • Journal Title: Pediatr Blood Cancer. 52(5) Pages: 591-595
  • Peer Reviewed
• [Journal Article] Severe hemorrhagic colitis caused by dasatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia (2009)
  • Author(s): Shimokaze T, Mitsui T, et al.
  • Journal Title: Pediatr Hematol Oncol. Volume: 26 Pages: 448-453
  • Peer Reviewed
• [Journal Article] Retrospective analysis of relapsed or primary refractory childhood lymphoblastic lymphoma in Japan (2009)
  • Author(s): Mitsui T, Mori T, et.al.
  • Journal Title: Pediatr Blood Cancer 52 Pages: 591-595
  • Peer Reviewed
• [Journal Article] Lymphoma Committee of the Japanese Pediatric Leukemia/Lymphoma Study Group. The role of hematopoietic stem cell transplantation with relapsed or primary refractory childhood B-cell non-Hodgkin lymphoma and mature B-cell leukemia : a retrospective analysis (2008)
  • Author(s): Fujita N, Mori T, Mitsui T, Inada H, Horibe K, Tsurusawa M
  • Journal Title: Pediatr Blood Cancer Volume: 51 Issue: 2 Pages: 88-92
  • DOI: 10.1002/pbc.21585
  • Peer Reviewed
• [Journal Article] 血液・腫瘍性疾患患児における抗真菌薬ミカファンギンの有効性に関する検討 (2008)
  • Author(s): 小沼正栄, 久間木悟, 吉成みやこ, 佐藤篤, 照井君典, 神尾卓哉, 平山雅士, 簡野美弥子, 川上貴子, 望月一弘, 伊藤正樹, 渡辺新, 遠藤幹也, 三井哲夫, 今泉益栄, 菊田敦, 伊藤悦朗, 土屋滋
  • Journal Title: 日小血会誌 Volume: 22 Pages: 226-232
  • NAID: 10029309484
  • Peer Reviewed
• [Journal Article] The role of hematopoietic stem cell transplantation with relapsed or primary refractory childhood B-cell non-Hodgkin lymphoma and mature B-cell leukemia : a retrospective analysis of enrolled cases in Japan. (2008)
  • Author(s): Fujita N, Mori T, Mitsui T, et al.
  • Journal Title: Pediatr Blood Cancer. 51(2) Pages: 188-92
  • Peer Reviewed
• [Journal Article] The role of hematopoietic stem cell transplantation with relapsed orprimary refractory childhood B-cell non-Hodgkin lymphoma and mature B-cell leukemia : a retrospective analysis of enrolled cases in Japan (2008)
  • Author(s): Fujita N, Mitsui T, et.al.
  • Journal Title: Pediatr Blood Cancer 51 Pages: 188-192
  • Peer Reviewed
• [Journal Article] 本邦におけるCharcot-Marie-Tooth病の特徴
  • Author(s): 早坂清, 阿部暁子
  • Journal Title: Annual review 2009神経 Pages: 218-225
• [Presentation] 髄芽腫で造血幹細胞移植を行なった3症例 (2010)
  • Author(s): 目黒亨、三井哲夫, ら
  • Organizer: 第26回日本小児がん学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-17
• [Presentation] G-CSFRの細胞外ドメインに変異を認めた先天性好中球減少症 (2009)
  • Author(s): 黒澤秀光, 三井哲夫ら, 他8名2番目
  • Organizer: 第51回日本小児血液学会総会
  • Place of Presentation: 浦安市東京ベイホテル東急
  • Year and Date: 2009-11-29
• [Presentation] G-CSF R細胞外ドメインに変異を認めた先天性好中球減少症 (2009)
  • Author(s): 黒澤秀光、三井哲夫, ら
  • Organizer: 第51回日本小児血液学会総会
• [Presentation] INSS分類Stage1で腫瘍全摘後無治療経過観察中、Stage4で再発した神経芽腫4歳女児 (2008)
  • Author(s): 三井哲夫, 川上貴子, 高橋憲幸, 金井雅代, 本間信夫, 仙道大, 簡野美弥子, 早坂清, 山際岩男, 江村隆起, 太田寛
  • Organizer: 第24回日本小児がん学会
  • Place of Presentation: 千葉市幕張メッセ国際会議場
  • Year and Date: 2008-11-16
• [Presentation] INSS分類Stage1で腫瘍全摘後無治療経過観察中、Stage4で再発した神経芽腫4歳女児 (2008)
  • Author(s): 三井哲夫ら
  • Organizer: 第24回日本小児がん学会
  • Place of Presentation: 千葉
  • Year and Date: 2008-11-16
• [Presentation] Philadelphia染色体陽性の急性骨髄性白血病(FAB M2)の10歳女児例 (2008)
  • Author(s): 目黒亨、三井哲夫ら
  • Organizer: 第50回日本小児血液学会
  • Place of Presentation: 千葉
  • Year and Date: 2008-11-14
• [Presentation] Refractory childhood lymphoblastic lymphoma : A retrospective analysis of relapsed or primary refractory cases in Japan (2008)
  • Author(s): Mitsui T, Mori T, Fujita T, Inada T, Horibe K, Tsurusawa M
  • Organizer: 19th annual meeting of the International BFM study group
  • Place of Presentation: Glasgow
  • Year and Date: 2008-03-05
• [Book] 小児白血病・リンパ腫の診療ガイドライン(日本小児血液学会編) (2011)
  • Author(s): 三井哲夫
  • Publisher: 金原出版,東京
• [Book] 小児感染症診療の落とし穴(尾内一信編) (2011)
  • Author(s): 三井哲夫
  • Publisher: 南江堂
• [Book] 小児白血病・リンパ腫の診療ガイドライン(日本小児血液学会編) (2011)
  • Author(s): 三井哲夫, ら
  • Publisher: 金原出版
• [Book] 抗菌薬・抗ウイルス薬の使い方(五十嵐隆編) (2009)
  • Author(s): 三井哲夫
  • Publisher: 中山書店