東北大学研究者紹介

研究者詳細

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日本語 English

顔写真

ナカノ　トモヒロ

中野　智太

Tomohiro Nakano

所属

病院　小児科　小児腫瘍科

職名

助教

学位

博士（医学）（東北大学）

researchmap

https://researchmap.jp/tomohiro_nakano

J-GLOBAL ID

202201005256795720

e-Rad 研究者番号

20968383

ORCID

https://orcid.org/0000-0001-9534-5121

経歴 9

2023年4月～継続中

東北大学病院　小児病態学分野　助教
2022年4月～ 2023年3月

東北大学　病院（医科診療部門）小児科　特任助手
2019年4月～ 2022年3月

東北大学　病院（医科診療部門）小児科　医員
2018年8月～ 2019年3月

石巻赤十字病院　小児科　医師
2018年4月～ 2018年7月

気仙沼市立病院　小児科　科長心得
2017年10月～ 2018年3月

仙台赤十字病院　新生児科　医師
2017年4月～ 2017年9月

東北大学病院　病院（医科診療部門）小児科　医員
2016年4月～ 2017年3月

岩手県立中部病院　小児科　医師
2014年4月～ 2016年3月

岩手県立中部病院　初期研修医

︎全件表示 ︎最初の5件までを表示

学歴 2

東北大学　大学院医学系研究科

2018年4月～ 2022年3月
東北大学　医学部　医学科

2008年4月～ 2014年3月

委員歴 4

日本小児がん研究グループ　CML委員会委員

2025年4月～継続中
日本小児がん研究グループ　リンパ腫委員会委員

2025年4月～継続中
日本免疫不全・自己炎症学会　PIDJ委員会委員

2025年2月～継続中
日本脳腫瘍学会　脳腫瘍診療ガイドライン委員会 SR委員

2024年11月～継続中

所属学協会 5

日本人類遺伝学会

2022年4月～継続中
日本血液学会

2020年～継続中
日本免疫不全・自己炎症学会

2019年～継続中
日本小児血液・がん学会

2017年～継続中
日本小児科学会

2016年～継続中

研究キーワード 3

臨床遺伝学
自己免疫・自己炎症疾患
小児がん

研究分野 2

ライフサイエンス / 遺伝学 /
ライフサイエンス / 血液、腫瘍内科学 /

受賞 2

第46回荒川記念賞

2022年11月　東北大学小児科同窓会
日本小児血液・がん学会優秀ポスター賞

2017年11月　日本小児血液・がん学会　本態性高Na血症を合併した神経節芽腫の一例

論文 30

Discovering patterns in the pathologic significance of non-missense deleterious variants in RELA. 国際誌

Hiroko Hayakawa, Miyuki Tsumura, Takanori Utsumi, Hiroshi Nihira, Wei-Te Lei, Ryo Ogino, Giorgia Bucciol, Tomohiro Nakano, Kiyoko Amo, Kunihiko Moriya, Seiichi Hayakawa, Yoko Mizoguchi, Shuhei Karakawa, You-Ning Lin, Han-Po Shih, Chia-Chi Lo, Sunita Janssenswillen, Sien Van Loo, Djalila Mekahli, Dusan Bogunovic, Stephanie Boisson-Dupuis, Kazushi Izawa, Cheng-Lung Ku, Takahiro Yasumi, Takaki Asano, Isabelle Meyts, Satoshi Okada

The Journal of allergy and clinical immunology　2026年3月13日

DOI： 10.1016/j.jaci.2026.01.020 　

詳細を見る詳細を閉じる

BACKGROUND: Monoallelic RELA variants resulting in haploinsufficiency (HI) have been linked to recurrent mucocutaneous ulcers and enteritis. Heterozygous RELA dominant-negative (DN) variants often exhibit autoinflammatory phenotypes associated with type I interferonopathy beyond those typically associated with RELA-HI variants. The vast majority of documented cases of autosomal dominant (AD) RelA deficiency are caused by non-missense deleterious variants introducing a premature stop codon. OBJECTIVE: We sought to characterize the clinical manifestations and pathologic significance of RELA variants and to establish the boundary separating RELA-HI and RELA-DN variants to facilitate position-based estimation of the nature of RELA variants. METHODS: RELA variants were characterized via a nuclear factor-κB reporter assay, immunoblotting, immunoprecipitation, and electrophoretic mobility shift assay in RELA and NFKB1 double knockout cells. RESULTS: Eight patients from 5 families with AD RelA deficiency were identified, and all harbored novel RELA variants. A comprehensive functional study using RELA nonsense variants identified amino acid P290 as the boundary between RELA-HI and RELA-DN variants in non-missense deleterious variants. In patients with RELA-DN variants, corticosteroid preparations were relatively ineffective, leading to increased use of biological drugs, mainly anti-TNF agents. We also identified atypical additional variants, including a missense variant and an in-frame variant, and experimentally confirmed their pathogenicity. CONCLUSIONS: The positions of non-missense deleterious variants in RELA allow the estimation of the associated functional changes, facilitating the precise diagnosis of AD RelA deficiency. Conversely, RELA missense variants require functional verification, as their impact cannot be predicted solely from their position.
重症複合免疫不全症様の臨床経過を辿った毛髪肝腸症候群の1例

成重勇太, 星雄介, 角田文彦, 桜井博毅, 田邊雄大, 小野頼母, 其田健司, 小泉沢, 武山淳二, 小寺麻実, 中野智太, 笹原洋二, 虻川大樹

日本小児科学会雑誌　129　(6)　854-854　2025年6月
出版者・発行元： (公社)日本小児科学会
ISSN：0001-6543

eISSN：2760-3180
Comprehensive genetic analysis for identification of monogenic disorders and selection of appropriate treatments in pediatric patients with persistent thrombocytopenia

Daichi Sato, Hinako Kirikae, Tomohiro Nakano, Saori Katayama, Hisao Yaoita, Jun Takayama, Gen Tamiya, Shigeo Kure, Atsuo Kikuchi, Yoji Sasahara

Pediatric Hematology and Oncology　2024年11月16日

DOI： 10.1080/08880018.2024.2395358 　
多発する大腸潰瘍を呈し,重症複合免疫不全症様の臨床経過を辿った毛髪肝腸症候群の1例

成重勇太, 星雄介, 角田文彦, 桜井博毅, 小泉沢, 武山淳二, 小寺麻実, 中野智太, 笹原洋二, 虻川大樹

日本小児栄養消化器肝臓学会雑誌　38　(Suppl.)　71-71　2024年10月
出版者・発行元： (一社)日本小児栄養消化器肝臓学会
ISSN：1346-9037
Efficacy of rituximab for the treatment and prevention of autoimmunity in patients with Wiskott-Aldrich syndrome and X-linked thrombocytopenia

Saori Katayama, Tomohiro Nakano, Tasuku Suzuki, Masahiro Irie, Hidetaka Niizuma, Atsuo Kikuchi, Yoji Sasahara

Clinical Immunology Communications　2024年6月

DOI： 10.1016/j.clicom.2024.04.002 　
治療後遠隔期に中枢神経外多発骨・骨髄転移再発を来した髄芽腫の一例

戒能明, 入江正寛, 岩淵蒼太, 中野智太, 鈴木資, 片山紗乙莉, 新妻秀剛, 下田由輝, 金森政之, 遠藤英徳, 笹原洋二, 菊池敦生

日本小児血液・がん学会雑誌　61　(1)　109-109　2024年5月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN：2187-011X

eISSN：2189-5384
持続性血小板減少症の小児患者における単一遺伝子疾患を同定するための包括的遺伝子解析

佐藤大地, 切替日奈子, 中野智太, 片山紗乙莉, 矢尾板久雄, 呉繁夫, 菊池敦生, 笹原洋二

日本小児科学会雑誌　128　(2)　267-267　2024年2月
出版者・発行元： (公社)日本小児科学会
ISSN：0001-6543
Human RELA dominant-negative mutations underlie type I interferonopathy with autoinflammation and autoimmunity. 国際誌査読有り

Kunihiko Moriya, Tomohiro Nakano, Yoshitaka Honda, Miyuki Tsumura, Masato Ogishi, Motoshi Sonoda, Masahiko Nishitani-Isa, Takashi Uchida, Mohamed Hbibi, Yoko Mizoguchi, Masataka Ishimura, Kazushi Izawa, Takaki Asano, Fumihiko Kakuta, Daiki Abukawa, Darawan Rinchai, Peng Zhang, Naotomo Kambe, Aziz Bousfiha, Takahiro Yasumi, Bertrand Boisson, Anne Puel, Jean-Laurent Casanova, Ryuta Nishikomori, Shouichi Ohga, Satoshi Okada, Yoji Sasahara, Shigeo Kure

The Journal of experimental medicine　220　(9)　2023年9月4日

DOI： 10.1084/jem.20212276 　

詳細を見る詳細を閉じる

Inborn errors of the NF-κB pathways underlie various clinical phenotypes in humans. Heterozygous germline loss-of-expression and loss-of-function mutations in RELA underlie RELA haploinsufficiency, which results in TNF-dependent chronic mucocutaneous ulceration and autoimmune hematological disorders. We here report six patients from five families with additional autoinflammatory and autoimmune manifestations. These patients are heterozygous for RELA mutations, all of which are in the 3' segment of the gene and create a premature stop codon. Truncated and loss-of-function RelA proteins are expressed in the patients' cells and exert a dominant-negative effect. Enhanced expression of TLR7 and MYD88 mRNA in plasmacytoid dendritic cells (pDCs) and non-pDC myeloid cells results in enhanced TLR7-driven secretion of type I/III interferons (IFNs) and interferon-stimulated gene expression in patient-derived leukocytes. Dominant-negative mutations in RELA thus underlie a novel form of type I interferonopathy with systemic autoinflammatory and autoimmune manifestations due to excessive IFN production, probably triggered by otherwise non-pathogenic TLR ligands.
肝芽腫を発症した21モノソミーモザイクの女児

庄司理以沙, 片山紗乙莉, 諸田真莉子, 中野智太, 鈴木資, 入江正寛, 新妻秀剛, 笹原洋二, 菊池敦生

日本小児血液・がん学会雑誌　60　(2)　167-168　2023年8月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN：2187-011X

eISSN：2189-5384
Two-year crizotinib monotherapy induced durable complete response of pediatric ALK-positive inflammatory myofibroblastic tumor. 国際誌

Akira Kaino, Hidetaka Niizuma, Saori Katayama, Masahiro Irie, Tomohiro Nakano, Daichi Sato, Tsuyoshi Saito, Shunsuke Kato, Yoshiyuki Suehara, Yoji Sasahara, Atsuo Kikuchi

Pediatric blood & cancer　70　(8)　e30330　2023年8月

DOI： 10.1002/pbc.30330 　
Reduced-intensity conditioning is effective for allogeneic hematopoietic stem cell transplantation in infants with MECOM-associated syndrome.

Masahiro Irie, Tetsuya Niihori, Tomohiro Nakano, Tasuku Suzuki, Saori Katayama, Kunihiko Moriya, Hidetaka Niizuma, Nobu Suzuki, Yuka Saito-Nanjo, Masaei Onuma, Takeshi Rikiishi, Atsushi Sato, Mayumi Hangai, Mitsuteru Hiwatari, Junji Ikeda, Reo Tanoshima, Norio Shiba, Yuki Yuza, Nobuyuki Yamamoto, Yoshiko Hashii, Motohiro Kato, Junko Takita, Miho Maeda, Yoko Aoki, Masue Imaizumi, Yoji Sasahara

International journal of hematology　117　(4)　598-606　2022年12月14日

DOI： 10.1007/s12185-022-03505-7 　

詳細を見る詳細を閉じる

Mutations in the MECOM encoding EVI1 are observed in infants who have radioulnar synostosis with amegakaryocytic thrombocytopenia. MECOM-associated syndrome was proposed based on clinical heterogeneity. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for progressive bone marrow failure. However, data regarding allogeneic HSCT for this rare disease are limited. We retrospectively assessed overall survival, conditioning regimen, regimen-related toxicities and long-term sequelae in six patients treated with allogeneic HSCT. All patients received a reduced-intensity conditioning (RIC) regimen consisting of fludarabine, cyclophosphamide or melphalan, and rabbit anti-thymocyte globulin and/or low-dose total body/thoracic-abdominal/total lymphoid irradiation, followed by allogeneic bone marrow or cord blood transplantation from unrelated donors between 4 and 18 months of age. All patients survived and achieved stable engraftment and complete chimerization with the donor type. Moreover, no patient experienced severe regimen-related toxicities, and only lower grades of acute graft-versus-host disease were observed. Three patients treated with low-dose irradiation had relatively short stature compared to three patients not treated with irradiation. Therefore, allogeneic HSCT with RIC is an effective and feasible treatment for infants with MECOM-associated syndrome. Future studies are needed to evaluate the use of low-dose irradiation to avoid risks of other long-term sequelae.
Type II pleuropulmonary blastoma with DICER1 mutation

Taichi Fukuzawa, Yuki Endo, Masahiro Irie, Hideyuki Sasaki, Hironori Kudo, Megumi Nakamura, Ryo Ando, Ryuji Okubo, Tsuyoshi Sakurai, Masatoshi Hashimoto, Keisuke Tada, Yudai Nakajima, Kosuke Sato, Ryoma Endo, Hidekazu Aoki, Saori Katayama, Tomohiro Nakano, Motoshi Wada

Journal of Pediatric Surgery Case Reports　87　102468-102468　2022年12月
出版者・発行元： Elsevier BV
DOI： 10.1016/j.epsc.2022.102468 　

ISSN：2213-5766
Comprehensive genomic profiling suggested multifocal development of retinoblastoma in a single eye. 国際誌

Miyu Sai, Hidetaka Niizuma, Kohei Yagi, Tomohiro Nakano, Saori Katayama, Noriko Himori, Masahiro Irie, Yoji Sasahara

Pediatric blood & cancer　e30031　2022年10月2日

DOI： 10.1002/pbc.30031 　
Clofarabine monotherapy in two patients with refractory Langerhans cell histiocytosis. 国際誌査読有り

Masahiro Irie, Tomohiro Nakano, Saori Katayama, Tasuku Suzuki, Kunihiko Moriya, Yuko Watanabe, Nobu Suzuki, Yuka Saitoh-Nanjyo, Masaei Onuma, Takeshi Rikiishi, Hidetaka Niizuma, Yoji Sasahara, Shigeo Kure

Cancer reports (Hoboken, N.J.)　5　(8)　e1579　2022年8月

DOI： 10.1002/cnr2.1579 　

詳細を見る詳細を閉じる

BACKGROUND: Better therapeutic options other than conventional chemotherapy for pediatric patients with refractory Langerhans cell histiocytosis (LCH) remain undetermined. CASE: We successfully treated two patients with refractory and risk organ negative LCH with clofarabine (CLO) monotherapy after recurrence. We administered total 23 courses of CLO monotherapy in patient 1 and 4 courses in patient 2. Both patients had distinct clinical manifestations but achieved a durable complete response with acceptable adverse effects of transient myelosuppression. CLO monotherapy was still effective when he had the second recurrent lesion after first completion of CLO in patient 1. We could discontinue prednisolone to control his refractory inflammation of LCH after completing CLO chemotherapy in patient 2. CONCLUSION: Although large-scale studies are warranted, CLO monotherapy could be a therapeutic option for high efficacy and feasibility besides other intensive combination chemotherapies or allogeneic hematopoietic stem cell transplantation for refractory LCH without risk organ involvement in children.
Novel POLE mutations identified in patients with IMAGE-I syndrome cause aberrant subcellular localisation and protein degradation in the nucleus. 国際誌査読有り

Tomohiro Nakano, Yoji Sasahara, Atsuo Kikuchi, Kunihiko Moriya, Hidetaka Niizuma, Tetsuya Niihori, Matsuyuki Shirota, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Shigeo Kure

Journal of medical genetics　59　(11)　1116-22　2022年5月9日

DOI： 10.1136/jmedgenet-2021-108300 　

詳細を見る詳細を閉じる

BACKGROUND: DNA replisome is a molecular complex that plays indispensable roles in normal DNA replication. IMAGE-I syndrome is a DNA replisome-associated genetic disease caused by biallelic mutations in the gene encoding DNA polymerase epsilon catalytic subunit 1 (POLE). However, the underlying molecular mechanisms remain largely unresolved. METHODS: The clinical manifestations in two patients with IMAGE-I syndrome were characterised. Whole-exome sequencing was performed and altered mRNA splicing and protein levels of POLE were determined. Subcellular localisation, cell cycle analysis and DNA replication stress were assessed using fibroblasts and peripheral blood from the patients and transfected cell lines to determine the functional significance of POLE mutations. RESULTS: Both patients presented with growth retardation, adrenal insufficiency, immunodeficiency and complicated diffuse large B-cell lymphoma. We identified three novel POLE mutations: namely, a deep intronic mutation, c.1226+234G>A, common in both patients, and missense (c.2593T>G) and in-frame deletion (c.711_713del) mutations in each patient. The unique deep intronic mutation produced aberrantly spliced mRNAs. All mutants showed significantly reduced, but not null, protein levels. Notably, the mutants showed severely diminished nuclear localisation, which was rescued by proteasome inhibitor treatment. Functional analysis revealed impairment of cell cycle progression and increase in the expression of phospho-H2A histone family member X in both patients. CONCLUSION: These findings provide new insights regarding the mechanism via which POLE mutants are highly susceptible to proteasome-dependent degradation in the nucleus, resulting in impaired DNA replication and cell cycle progression, a characteristic of DNA replisome-associated diseases.
Refractory T-cell/histiocyte-rich large B-cell lymphoma in a patient with ataxia-telangiectasia caused by novel compound heterozygous variants in ATM. 査読有り

Daichi Sato, Kunihiko Moriya, Tomohiro Nakano, Chihiro Miyagawa, Saori Katayama, Hidetaka Niizuma, Yoji Sasahara, Shigeo Kure

International journal of hematology　114　(6)　735-741　2021年12月

DOI： 10.1007/s12185-021-03203-w 　

詳細を見る詳細を閉じる

Ataxia-telangiectasia (A-T) is an autosomal recessive chromosomal breakage syndrome caused by mutation of the ATM (A-T mutated) gene, which encodes a protein kinase that has a major role in the cellular response to DNA damage. Approximately, 10% of A-T patients develop lymphoid malignancies. Deaths caused by extreme sensitivity to chemotherapy for malignancy have been reported, and cancer treatment in A-T is extraordinarily difficult, needing careful monitoring and individualized protocols. We report the case of a 12-year-old girl with A-T diagnosed at the age of 3 in association with IgA deficiency and recurrent pulmonary infections. Sanger sequencing revealed compound heterozygosity of the ATM gene, which bore two novel mutations. At the age of 12, she developed stage IV T-cell/histiocyte-rich large B-cell lymphoma. The tumor was resistant to chemotherapy, and she unfortunately died of cardiac insufficiency and multiple organ failure induced by rapid progression of the disease. The treatment approach for children with A-T and advanced-stage B-non-Hodgkin lymphoma must be refined.
びまん性大細胞型B細胞性リンパ腫を合併し、治療に難渋した毛細血管拡張性運動失調症の一例(Ataxia-telangiectasia with refractory diffuse large B cell lymphoma caused by novel compound heterozygous ATM variants)

Sato Daichi, Moriya Kunihiko, Nakano Tomohiro, Katayama Saori, Niizuma Hidetaka, Sasahara Yoji, Kure Shigeo

日本小児血液・がん学会雑誌　58　(4)　199-199　2021年10月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN：2187-011X

eISSN：2189-5384
新規TSC2遺伝子変異とTP53の体細胞性変異により骨肉腫を発症した1例(A pediatric case of osteosarcoma and tuberous sclerosis complex with a somatic mutation in the TP53 gene)

Moriya Kunihiko, Sato Daichi, Nakano Tomohiro, Watanuki Munenori, Katayama Saori, Niizuma Hidetaka, Sasahara Yoji, Kure Shigeo

日本小児血液・がん学会雑誌　58　(4)　233-233　2021年10月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN：2187-011X

eISSN：2189-5384
同種骨髄移植後、肝類洞閉塞症候群とITPが合併した骨髄異形成症候群の8歳女児例(A case report of 8 year-old girl with MDS, suffering from SOS after allogeneic BMT, followed by post-transplantation thrombocytopenia)

Irie Masahiro, Sasahara Yoji, Nakano Tomohiro, Suzuki Tasuku, Katayama Saori, Moriya Kunihiko, Niizuma Hidetaka, Rikiishi Takeshi, Hirayama Masashi, Kure Shigeo

日本小児血液・がん学会雑誌　58　(4)　247-247　2021年10月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN：2187-011X

eISSN：2189-5384
LRBA遺伝子の新規複合ヘテロ変異を伴い、乳児期に発症した劇症1型糖尿病の1例(Infantile-onset fulminant type 1 diabetes mellitus caused by novel compound heterozygous LRBA variants)

Kaino Akira, Moriya Kunihiko, Nakano Tomohiro, Sato Daichi, Katayama Saori, Niizuma Hidetaka, Sasahara Yoji, Kure Shigeo

日本小児血液・がん学会雑誌　58　(4)　260-260　2021年10月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN：2187-011X

eISSN：2189-5384
A pediatric case of osteosarcoma and tuberous sclerosis complex with a novel germline mutation in the TSC2 gene and a somatic mutation in the TP53 gene. 国際誌査読有り

Kaoru Kuroda, Kunihiko Moriya, Tomohiro Nakano, Ryoko Saito, Daichi Sato, Saori Katayama, Hidetaka Niizuma, Munenori Watanuki, Mitsugu Uematsu, Yoji Sasahara, Shigeo Kure

Pediatric blood & cancer　68　(6)　e28960　2021年6月

DOI： 10.1002/pbc.28960 　
RelAの優性阻害変異により,自己炎症や自己免疫疾患をきたす(Dominant negative RelA mutation causes autoinflammatory and autoimmune disorders)

森谷邦彦, 中野智太, 本田吉孝, 園田素史, 津村弥来, 内田崇, 石村匡崇, 井澤和司, 角田文彦, 虻川大樹, 八角高裕, 岡田賢, 大賀正一, 笹原洋二, 呉繁夫

日本小児科学会雑誌　125　(2)　301-301　2021年2月
出版者・発行元： (公社)日本小児科学会
ISSN：0001-6543
Case Report: Infantile-Onset Fulminant Type 1 Diabetes Mellitus Caused by Novel Compound Heterozygous LRBA Variants. 国際誌査読有り

Eriko Totsune, Tomohiro Nakano, Kunihiko Moriya, Daichi Sato, Dai Suzuki, Akinobu Miura, Saori Katayama, Hidetaka Niizuma, Junko Kanno, Menno C van Zelm, Kohsuke Imai, Hirokazu Kanegane, Yoji Sasahara, Shigeo Kure

Frontiers in immunology　12　677572-677572　2021年

DOI： 10.3389/fimmu.2021.677572 　

詳細を見る詳細を閉じる

Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency is a subtype of common variable immune deficiency (CVID). Numerous case reports and cohort studies have described a broad spectrum of clinical manifestations and variable disease phenotypes, including immune dysregulation, enteropathy, and recurrent infections. Although LRBA deficiency is an autosomal recessive primary immunodeficiency resulting in a phenotype similar to CVID, it is a monogenic disease and separate from CVID. Recently, in a report of monogenic primary immunodeficiency disorder associated with CVID and autoimmunity, the most common mutated gene was LRBA. We report the case of a girl who presented with fulminant type 1 diabetes at age 7 months. She later experienced recurrent bacterial infections with neutropenia and idiopathic thrombocytopenic purpura. Clinical genome sequencing revealed compound heterozygosity of the LRBA gene, which bore two novel mutations. A genetic basis should be considered in the differential diagnosis for very young patients with fulminant autoimmunity, and the diagnostic work-up should include evaluation of markers of immunodeficiency.
がん遺伝子パネル検査を施行した小児がん20例の検討診断・治療に関する有用性(Clinical sequencing of 20 pediatric solid tumors: utility for molecular diagnosis and targeted therapy)

Niizuma Hidetaka, Kaino Akira, Nakano Tomohiro, Katayama Saori, Moriya Kunihiko, Irie Masahiro, Rikiishi Takeshi, Sasahara Yoji, Kure Shigeo

日本小児血液・がん学会雑誌　57　(4)　242-242　2020年10月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN：2187-011X

eISSN：2189-5384
RNA-Seqにより原因遺伝子検索を行った骨髄増殖性腫瘍合併ETP-LBLの一例(Genetic analysis of an early T-cell precursor acute lymphoblastic lymphoma associated with myeloproliferative neoplasm)

Katayama Saori, Nakano Tomohiro, Irie Masahiro, Moriya Kunihiko, Niizuma Hidetaka, Rikiishi Takeshi, Sasahara Yoji, Kure Shigeo

日本小児血液・がん学会雑誌　57　(4)　226-226　2020年10月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN：2187-011X

eISSN：2189-5384
Ruxolitinib treatment of a patient with steroid-dependent severe autoimmunity due to STAT1 gain-of-function mutation. 査読有り

Kunihiko Moriya, Tasuku Suzuki, Nao Uchida, Tomohiro Nakano, Saori Katayama, Masahiro Irie, Takeshi Rikiishi, Hidetaka Niizuma, Satoshi Okada, Kohsuke Imai, Yoji Sasahara, Shigeo Kure

International journal of hematology　112　(2)　258-262　2020年8月

DOI： 10.1007/s12185-020-02860-7 　

詳細を見る詳細を閉じる

Signal transducer and activator of transcription 1 gain-of-function (STAT1 GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC). We report the effect of oral ruxolitinib, an inhibitor of Janus kinase (JAK) family tyrosine kinases, on the clinical and immune status of a 3-year-old male with steroid-dependent severe autoimmunity due to a STAT1 GOF T385M mutation. The patient's susceptibility to infection improved with antimicrobial prophylaxis and immunoglobulin replacement therapy, but he continued to exhibit severely disabling symptoms of autoimmunity. More than one-third of patients with STAT1 GOF mutations present with autoimmune manifestations, and this patient's mutation was reported to cause CMC with autoimmunity. We analyzed the interleukin (IL)-17A and IFN-γ levels and immunophenotype by flow cytometry before and during treatment with ruxolitinib. The peripheral IL-17A level did not increase, but the IFN-γ level decreased after 4 months of therapy. The STAT1 phosphorylation level decreased significantly upon stimulation of patient cells with IFN-γ. Clinically, cytomegalovirus reactivation occurred, but was controlled. No other adverse effect was noted. We report the potential of JAK1/2 inhibition with ruxolitinib for both CMC and steroid-dependent autoimmunity. However, long-term administration is necessary, as the effect is not sustained after treatment is discontinued.
Correction to: the IL1RN Mutation Creating the Most-Upstream Premature Stop Codon Is Hypomorphic because of a Reinitiation of Translation. 国際誌査読有り

Kunihiko Moriya, Saori Kadowaki, Tomohiro Nakano, Sanem E Akarcan, Necil Kutukculer, Guzide Aksu, Yoji Sasahara, Shigeo Kure, Hidenori Ohnishi, Jean-Laurent Casanova, Anne Puel, Toshiyuki Fukao

Journal of clinical immunology　40　(4)　646-646　2020年5月

DOI： 10.1007/s10875-020-00776-9 　

詳細を見る詳細を閉じる

The original version of our manuscript, entitled, " The IL1RN mutation creating the most-upstream premature stop codon is hypomorphic because of a reinitiation of translation" unfortunately contained mistakes in Fig. 1a and d legends. The text should read as follows.
Wiskott-Aldrich症候群に合併した全身性自己免疫性炎症にRituximabが奏効した一例査読有り

中野智太, 新妻秀剛, 片山紗乙莉, 渡辺祐子, 入江正寛, 力石健, 笹原洋二, 呉繁夫

日本小児血液・がん学会雑誌　56　(2)　221-224　2019年9月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN：2187-011X

eISSN：2189-5384
Acquisition of chemoresistance to gemcitabine is induced by a loss-of-function missense mutation of DCK. 国際誌査読有り

Tomohiro Nakano, Yuriko Saiki, Chiharu Kudo, Akiyoshi Hirayama, Yasuhiko Mizuguchi, Sho Fujiwara, Tomoyoshi Soga, Makoto Sunamura, Nobutoshi Matsumura, Fuyuhiko Motoi, Michiaki Unno, Akira Horii

Biochemical and biophysical research communications　464　(4)　1084-1089　2015年9月4日

DOI： 10.1016/j.bbrc.2015.07.080 　

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The anti-tumor activity of gemcitabine (GEM) has been clinically proven in several solid tumors, including pancreatic cancer, biliary tract cancer, urinary bladder cancer, and non-small cell lung cancer. However, problems remain with issues such as acquisition of chemoresistance against GEM. GEM is activated after phosphorylation by deoxycytidine kinase (DCK) inside of the cell; thus, DCK inactivation is one of the important mechanisms for acquisition of GEM resistance. We previously investigated the DCK gene in multiple GEM resistant cancer cell lines and identified frequent inactivating mutations. In this study, we identified two crucial genetic alteration in DCK. (1) A total deletion of DCK in RTGBC1-TKB, an acquired GEM resistant cell line derived from a gall bladder cancer cell line TGBC1-TKB. (2) An E197K missense alteration of DCK in MKN28, a gastric cancer cell line; its acquired GEM resistant cancer cell line, RMKN28, showed a loss of the normal E197 allele. We introduced either normal DCK or altered DCK_E197K into RMKN28 and proved that only the introduction of normal DCK restored GEM sensitivity. Furthermore, we analyzed 104 healthy volunteers and found that none of them carried the same base substitution observed in MKN28. These results strongly suggest that (1) the E197K alteration in DCK causes inactivation of DCK, and that (2) loss of the normal E197 allele is the crucial mechanism in acquisition of GEM resistance in RMKN28.
DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells. 国際誌査読有り

Yuriko Saiki, Yuki Yoshino, Hiroko Fujimura, Tatsuya Manabe, Yuki Kudo, Miki Shimada, Nariyasu Mano, Tomohiro Nakano, Yoonha Lee, Shinjiro Shimizu, Shinya Oba, Sho Fujiwara, Hideyuki Shimizu, Na Chen, Zhaleh Kashkouli Nezhad, Guo Jin, Shinichi Fukushige, Makoto Sunamura, Masaharu Ishida, Fuyuhiko Motoi, Shinichi Egawa, Michiaki Unno, Akira Horii

Biochemical and biophysical research communications　421　(1)　98-104　2012年4月27日

DOI： 10.1016/j.bbrc.2012.03.122 　

詳細を見る詳細を閉じる

Although gemcitabine is the most effective chemotherapeutic agent against pancreatic cancer, a growing concern is that a substantial number of patients acquire gemcitabine chemoresistance. To elucidate the mechanisms of acquisition of gemcitabine resistance, we developed gemcitabine-resistant cell lines from six human cancer cell lines; three pancreatic, one gastric, one colon, and one bile duct cancer. We first analyzed gemcitabine uptake using three paired parental and gemcitabine resistant pancreatic cancer cell lines (PK-1 and RPK-1, PK-9 and RPK-9, PK-59 and RPK-59) and found that uptake of gemcitabine was rapid. However, no DNA damage was induced in resistant cells. We further examined the microarray-based expression profiles of the cells to identify genes associated with gemcitabine resistance and found a remarkable reduction in the expression of deoxycytidine kinase (DCK). DCK is a key enzyme that activates gemcitabine by phosphorylation. Genetic alterations and expression of DCK were studied in these paired parental and derived gemcitabine-resistant cell lines, and inactivating mutations were found only in gemcitabine-resistant cell lines. Furthermore, siRNA-mediated knockdown of DCK in the parental cell lines yielded gemcitabine resistance, and introduction of DCK into gemcitabine-resistant cell lines invariably restored gemcitabine sensitivities. Mutation analyses were expanded to three other different paired cell lines, DLD-1 and RDLD-1 (colon cancer cell line), MKN-28 and RMKN-28 (gastric cancer cell line), and TFK-1 and RTFK -1 (cholangiocarcinoma cell line). We found inactivating mutations in RDLD-1 and RTFK-1 and decreased expression of DCK in RMKN-28. These results indicate that the inactivation of DCK is one of the crucial mechanisms in acquisition of gemcitabine resistance.

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MISC 29

Genomic characteristics of diffuse large B-cell lymphoma associated with Wiskott-Aldrich syndrome

Asami Kodera, Tomohiro Nakano, Hidehiro Minegishi, Akira Kaino, Daichi Sato, Hitomi Abe, Saori Katayama, Masahiro Irie, Hidetaka Niizuma, Yoji Sasahara

BLOOD　146　5317-5318　2025年11月3日

DOI： 10.1182/blood-2025-5317 　

ISSN： 0006-4971

eISSN： 1528-0020
肉眼的血尿と紫斑を主訴とし,Evans症候群と膜性腎症を合併した幼児例

森ひろみ, 内田奈生, 中野智太, 鈴木資, 片山紗乙莉, 入江正寛, 新妻秀剛, 笹原洋二, 菊池敦生

日本小児腎臓病学会雑誌(Web)　37　2024年

ISSN： 1881-3933
治療後遠隔期に中枢神経外多発骨・骨髄転移再発を来した髄芽腫の一例

戒能明, 入江正寛, 岩淵蒼太, 中野智太, 鈴木資, 片山紗乙莉, 新妻秀剛, 下田由輝, 金森政之, 遠藤英徳, 笹原洋二, 菊池敦生

日本小児血液・がん学会雑誌(Web)　61　(1)　2024年

ISSN： 2189-5384
肝芽腫を発症した21モノソミーモザイクの女児

庄司理以沙, 片山紗乙莉, 諸田真莉子, 中野智太, 鈴木資, 入江正寛, 新妻秀剛, 笹原洋二, 菊池敦生

日本小児血液・がん学会雑誌(Web)　60　(2)　2023年

ISSN： 2189-5384
新規POLE遺伝子変異を有するIMAGE-I症候群2症例の病態解析

中野智太, 森谷邦彦, 菊池敦生, 新妻秀剛, 笹原洋二, 舟山亮, 中山啓子, 城田松之, 新堀哲也, 青木洋子, 呉繁夫

日本免疫不全・自己炎症学会雑誌(Web)　2　(2)　2023年

ISSN： 2435-7693
腫瘍検体でDICER1変異を同定した胸膜肺芽腫の一例

中野智太, 鈴木資, 片山紗乙莉, 入江正寛, 福澤太一, 新妻秀剛, 笹原洋二

日本小児血液・がん学会雑誌　59　(2)　204-204　2022年7月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN： 2187-011X

eISSN： 2189-5384
MEFV遺伝子関連腸炎2例の臨床経過

加藤歩, 中野智太, 星雄介, 角田文彦, 笹原洋二, 虻川大樹

日本小児栄養消化器肝臓学会雑誌　36　(1)　44-44　2022年4月
出版者・発行元： (一社)日本小児栄養消化器肝臓学会
ISSN： 1346-9037
MEFV遺伝子関連腸炎2例の臨床経過

加藤歩, 中野智太, 星雄介, 角田文彦, 笹原洋二, 虻川大樹

日本小児栄養消化器肝臓学会雑誌　36　(1)　44-44　2022年4月
出版者・発行元： (一社)日本小児栄養消化器肝臓学会
ISSN： 1346-9037
自己炎症性疾患および自己免疫性疾患を引き起こすI型インターフェロノパシーの背景には,ヒトRELAのドミナントネガティブ変異がある

MORIYA Kunihiko, NAKANO Tomohiro, HONDA Yoshitaka, TSUMURA Miyuki, SONODA Motoshi, ISA-NISHITANI Masahiko, UCHIDA Takashi, MIZUGUCHI Yoko, ISHIMURA Masataka, IZAWA Kazushi, KAKUTA Fumihiko, ABUKAWA Daiki, YASUMI Takahiro, NISHIKOMORI Ryuta, OHGA Shouichi, OKADA Satoshi, SASAHARA Yoji, KURE Shigeo

日本免疫不全・自己炎症学会雑誌(Web)　1　(2)　2022年

ISSN： 2435-7693
IMAGE-I症候群における新規POLE遺伝子変異の同定とその病態解析

中野智太, 笹原洋二, 菊池敦生, 森谷邦彦, 新妻秀剛, 呉繁夫

日本人類遺伝学会大会プログラム・抄録集　67th (CD-ROM)　2022年
A Case Report of 8 Year-Old Girl with MDS, Suffering from SOS After Allogeneic BMT, Followed by Post-Transplantation Thrombocytopenia

Masahiro Irie, Yoji Sasahara, Tomohiro Nakano, Tasuku Suzuki, Saori Katayama, Kunihiko Moriya, Hidetaka Niizuma, Takeshi Rikiishi, Masashi Hirayama, Shigeo Kure

PEDIATRIC BLOOD & CANCER　68　2021年11月

ISSN： 1545-5009

eISSN： 1545-5017
Infantile-Onset Fulminant Type 1 Diabetes Mellitus Caused by Novel Compound Heterozygous Lrba Variants

Akira Kaino, Kunihiko Moriya, Tomohiro Nakano, Daichi Sato, Saori Katayama, Hidetaka Niizuma, Yoji Sasahara, Shigeo Kure

PEDIATRIC BLOOD & CANCER　68　2021年11月

ISSN： 1545-5009

eISSN： 1545-5017
LRBA deficiency presenting with infantile fulminant type I diabetes mellitus(和訳中)

森谷邦彦, 戸恒恵理子, 中野智太, 佐藤大地, 片山紗乙莉, 新妻秀剛, 笹原洋二, 呉繁夫

日本血液学会学術集会　83回　PS-4　2021年9月
出版者・発行元： (一社)日本血液学会
乳児期に劇症1型糖尿病で発症したLRBA欠損症の一例(LRBA deficiency presenting with infantile fulminant type I diabetes mellitus)

森谷邦彦, 戸恒恵理子, 中野智太, 佐藤大地, 片山紗乙莉, 新妻秀剛, 笹原洋二, 呉繁夫

日本血液学会学術集会　83回　PS-4　2021年9月
出版者・発行元： (一社)日本血液学会
RelAの優性阻害変異により,自己炎症や自己免疫疾患をきたす(Dominant negative RelA mutation causes autoinflammatory and autoimmune disorders)

森谷邦彦, 中野智太, 本田吉孝, 園田素史, 津村弥来, 内田崇, 石村匡崇, 井澤和司, 角田文彦, 虻川大樹, 八角高裕, 岡田賢, 大賀正一, 笹原洋二, 呉繁夫

日本小児科学会雑誌　125　(2)　301-301　2021年2月
出版者・発行元： (公社)日本小児科学会
ISSN： 0001-6543
新規TSC2遺伝子変異とTP53の体細胞性変異により骨肉腫を発症した1例

MORIYA Kunihiko, SATO Daichi, NAKANO Tomohiro, WATANUKI Munenori, KATAYAMA Saori, NIIZUMA Hidetaka, SASAHARA Yoji, KURE Shigeo

日本小児血液・がん学会雑誌(Web)　58　(4)　2021年

ISSN： 2189-5384
同種骨髄移植後,肝類洞閉塞症候群とITPが合併した骨髄異形成症候群の8歳女児例

IRIE Masahiro, SASAHARA Yoji, NAKANO Tomohiro, SUZUKI Tasuku, KATAYAMA Saori, MORIYA Kunihiko, NIIZUMA Hidetaka, RIKIISHI Takeshi, HIRAYAMA Masashi, KURE Shigeo

日本小児血液・がん学会雑誌(Web)　58　(4)　2021年

ISSN： 2189-5384
びまん性大細胞型B細胞性リンパ腫を合併し,治療に難渋した毛細血管拡張性運動失調症の一例

SATO Daichi, MORIYA Kunihiko, NAKANO Tomohiro, KATAYAMA Saori, NIIZUMA Hidetaka, SASAHARA Yoji, KURE Shigeo

日本小児血液・がん学会雑誌(Web)　58　(4)　2021年

ISSN： 2189-5384
Genetic Analysis of an Early T-Cell Precursor Acute Lymphoblastic Lymphoma Associated with Myeloproliferative Neoplasm

Saori Katayama, Tomohiro Nakano, Masahiro Irie, Kunihiko Moriya, Hidetaka Niizuma, Takeshi Rikiishi, Yoji Sasahara, Shigeo Kure

PEDIATRIC BLOOD & CANCER　67　2020年12月

ISSN： 1545-5009

eISSN： 1545-5017
Clinical Sequencing of 20 Pediatric Solid Tumors: Utility for Molecular Diagnosis and Targeted Therapy

Hidetaka Niizuma, Akira Kaino, Tomohiro Nakano, Saori Katayama, Kunihiko Moriya, Masahiro Irie, Takeshi Rikiishi, Yoji Sasahara, Shigeo Kure

PEDIATRIC BLOOD & CANCER　67　2020年12月

ISSN： 1545-5009

eISSN： 1545-5017
再発CD30陽性縦隔原発大細胞性B細胞性リンパ腫(PMLBL)に対してbrentuximab vedotin単剤療法が著効した1例

入江正寛, 中野智太, 片山紗乙莉, 森谷邦彦, 渡辺祐子, 新妻秀剛, 力石健, 笹原洋二, 呉繁夫, 渡辺みか

臨床血液　60　(11)　1593-1593　2019年11月
出版者・発行元： (一社)日本血液学会-東京事務局
ISSN： 0485-1439

eISSN： 1882-0824
免疫不全新規のヒトNF-κB経路の先天性障害(Novel Human Inborn Errors of the NF-κB Pathway)

Moriya Kunihiko, Nguyen Tina, Celmeli Fatih, Uchida Takashi, Nakano Tomohiro, Kakuta Fumihiko, Abukawa Daiki, Beziat Vivien, Okada Satoshi, Imai Kohsuke, Tangye Stuart G., 笹原洋二, Puel Anne, Casanova Jean-Laurent

日本臨床免疫学会総会プログラム・抄録集　47回　80-80　2019年10月
出版者・発行元： (一社)日本臨床免疫学会
Clinical and Genetic Analysis of two Patients with ACTH Unresponsiveness, NK Cell Deficiency and Diffuse Large B Cell Lymphoma

Yoji Sasahara, Tomohiro Nakano, Saori Katayama, Tasuku Suzuki, Yuko Watanabe, Masahiro Irie, Hidetaka Niizuma, Takeshi Rikiishi, Shigeo Kure

PEDIATRIC BLOOD & CANCER　64　S41-S41　2017年11月

ISSN： 1545-5009

eISSN： 1545-5017
A report of 2 Patients with Therapy-refractory Langerhans Cell Histiocytosis (LCH) who were Successfully Treated with Monotherapy of Clofarabine

Masahiro Irie, Tomohiro Nakano, Tasuku Suzuki, Saori Katayama, Yuko Watanabe, Hidetaka Niizuma, Takeshi Rikiishi, Yoji Sasahara, Shigeo Kure

PEDIATRIC BLOOD & CANCER　64　S34-S35　2017年11月

ISSN： 1545-5009

eISSN： 1545-5017
本態性高Na血症を合併した神経節芽腫の一例

中野智太, 新妻秀剛, 片山沙乙莉, 渡辺祐子, 入江正寛, 力石健, 笹原洋二, 呉繁夫, 風間理郎, 渡辺みか

日本小児血液・がん学会雑誌　54　(4)　368-368　2017年10月
出版者・発行元： (一社)日本小児血液・がん学会
ISSN： 2187-011X

eISSN： 2189-5384
乳児特発性間質性肺疾患の1例

中野智太, 滝沢友里恵, 遠野千佳子, 越前屋竹寅

日本小児科学会雑誌　121　(8)　1447-1448　2017年8月
出版者・発行元： (公社)日本小児科学会
ISSN： 0001-6543
Traumatic retroclival epidural hematomaの幼児例

小笠原靖, 樫村博史, 吉田純, 麻生謙太, 中野智太

岩手県立病院医学会雑誌　57　(1)　55-58　2017年7月
出版者・発行元：岩手県立病院医学会
ISSN： 0385-9320
ヒトパルボウイルスB19感染により類白血病反応を呈した不安定ヘモグロビン症の1例

中野智太, 滝沢友里恵, 遠野千佳子, 越前屋竹寅

日本小児科学会雑誌　121　(6)　1106-1106　2017年6月
出版者・発行元： (公社)日本小児科学会
ISSN： 0001-6543
Human cancer cells acquire chemoresistance to gemcitabine mainly through loss-of-function mutations in the DCK gene

Akira Horii, Yuriko Saiki, Tomohiro Nakano, Chiharu Kudo, Makoto Sunamura

CANCER RESEARCH　75　2015年8月

DOI： 10.1158/1538-7445.AM2015-5473 　

ISSN： 0008-5472

eISSN： 1538-7445

︎全件表示 ︎最初の5件までを表示

講演・口頭発表等 2

びまん性大細胞型B細胞性リンパ腫を合併したWiskott-Aldrich症候群2症例の検討

中野智太

第3回日本免疫不全・自己炎症学会総会・学術集会　2020年2月15日
ステロイド抵抗性急性GVHDに対してMTXが有効であったWiskott-Aldrich症候群の一例

中野智太

第31回東北BMT研究会　2018年6月30日

共同研究・競争的資金等の研究課題 1

DNAポリメラーゼεの異常によるIMAGE-I症候群の病態解明

中野智太

2023年4月1日～ 2025年3月31日

詳細を見る詳細を閉じる

現在、IMAGE-I症候群の患者から樹立した線維芽細胞の解析、また新規患者・類似患者の集積と解析を主におこなっている。IMAGE-I症候群の患者由来の線維芽細胞の解析では、健常人由来の線維芽細胞で行われているDNA合成との違いを確認するため、トランスクリプトーム解析を実施し、DNAポリメラーゼεを構成する各遺伝子や、その他のDNA複製に関わる遺伝子の発現の違いを確認した。変異POLE蛋白の解析はあまり進められていないが、現時点ではDNA伸長反応には大きな違いがないことを確認している。新規患者・類似患者の集積では、IMAGE-I症候群の新規患者は見つかっていないものの、DNAポリメラーゼεの構成するサブユニットで、POLE遺伝子とは異なる遺伝子異常（遺伝子X）による類似患者を同定した。同患者より単離した皮膚線維芽細胞の樹立に成功し、DNA複製関連疾患に特徴的な細胞周期の異常を証明した。また、この線維芽細胞を用いたトランスクリプトーム解析を実施し、IMAGE-I症候群の患者由来細胞との比較を行った。現在は遺伝子Xの異常によって生じる変異蛋白の発現系を作成しており、異常蛋白の病原性について解析を進めている。遺伝子Xの異常によって生じる疾患は世界的に非常に稀少であり、詳細に解析された報告は存在しない。本患者の臨床像と患者細胞を解析し報告することは、同じDNAポリメラーゼεの異常によるIMAGE-I症候群の理解だけでなく、DNA複製関連疾患の病態理解に貢献し得るものと考えている。