小児血液・腫瘍研究部

研究部紹介

小児血液・腫瘍研究部では、小児がんの分子特性の解析を通じて、発症および病態形成のメカニズムの解明や新規診断・治療法の開発に貢献することを目指しています。小児がんは、小児の死因の上位を占めていますが、正しい診断に基づく適切な治療によって多くの症例で治癒を望み得ること、治療終了後に思春期や成人期を向かえるため治療に伴う晩期障害等の多くの問題を生じる場合が多いことなどから、重要な成育疾患の一つです。また、小児がんは、成人のがんとは異なり、出生、発育、成長に伴う組織の発生や細胞の分化の機構の破綻と密接に関係しているなどの独自の特徴があります。そこで当部では、小児がんの遺伝子や蛋白の発現の特徴や異常、各分子の機能とがんの生物学的特性との関係などの基礎研究を行っています。

研究内容

当部には2つの研究室があります。造血腫瘍発生研究室では、発生異常の視点から小児がんをとらえて研究をしています。白血病を始めとする小児がんがどうやって、そして、なぜ発病するのか、その問いに答えることに挑戦しています。分子病理研究室では、小児腎腫瘍や神経芽腫、Ewing肉腫等の固形腫瘍を中心に、遺伝子の異常と腫瘍の発生・進展との関連について研究し、新たな診断法や治療法の開発を目指しています。

また、当部の重要な役割として、研究の成果や技術を活かし、白血病のマーカー診断や固形腫瘍の遺伝子診断など、我が国の小児がんの治療研究における中央診断の様々な部分を担当しており、迅速で詳細な検査結果を各診療施設に提供することを目標にしています。
以上の研究を通じ、小児がんの診療の向上に貢献したいと考えています。

スタッフ

業績

2021

1. den Boer ML, Cario G, Moorman AV, Boer JM, de Groot-Kruseman HA, Fiocco M, Escherich G, Imamura T, Yeoh A, Sutton R, Dalla-Pozza L, Kiyokawa N, Schrappe M, Roberts KG, Mullighan CG, Hunger SP, Vora A, Attarbaschi A, Zaliova M, Elitzur S, Cazzaniga G, Biondi A, Loh ML, Pieters R; Ponte di Legno Childhood ALL Working Group. Outcomes of paediatric patients with B-cell acute lymphocytic leukaemia with ABL-class fusion in the pre-tyrosine-kinase inhibitor era: a multicentre, retrospective, cohort study. Lancet Haematol. 2021 Jan;8(1):e55-e66.

2020

1. Ohki K, Takahashi H, Fukushima T, Nanmoku T, Kusano S, Mori M, Nakazawa Y, Yuza Y, Migita M, Okuno H, Morimoto A, Yoshino H, Kato M, Hayashi Y, Manabe A, Ohara A, Hasegawa D, Inukai T, Tomizawa D, Koh K, Kiyokawa N; Tokyo Children's Cancer Study Group (TCCSG). Impact of immunophenotypic characteristics on genetic subgrouping in childhood acute lymphoblastic leukemia: Tokyo Children's Cancer Study Group (TCCSG) study L04-16. Genes Chromosomes Cancer. 2020 Oct;59(10):551-561.
2. Shirai R, Osumi T, Terashima K, Kiyotani C, Uchiyama M, Tsujimoto S, Yoshida M, Yoshida K, Uchiyama T, Tomizawa D, Shioda Y, Sekiguchi M, Watanabe K, Keino D, Ueno-Yokohata H, Ohki K, Takita J, Ito S, Deguchi T, Kiyokawa N, Ogiwara H, Hishiki T, Ogawa S, Okita H, Matsumoto K, Yoshioka T, Kato M. High prevalence of SMARCB1 constitutional abnormalities including mosaicism in malignant rhabdoid tumors. Eur J Hum Genet. 2020 Aug;28(8):1124-1128.
3. Yoshida M, Tanase-Nakao K, Shima H, Shirai R, Yoshida K, Osumi T, Deguchi T, Mori M, Arakawa Y, Takagi M, Miyamura T, Sakaguchi K, Toyoda H, Ishida H, Sakata N, Imamura T, Kawahara Y, Morimoto A, Koike T, Yagasaki H, Ito S, Tomizawa D, Kiyokawa N, Narumi S, Kato M.Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7. Br J Haematol. 2020 Dec;191(5):835-843.
4. Ueno H, Yoshida K, Shiozawa Y, Nannya Y, Iijima-Yamashita Y, Kiyokawa N, Shiraishi Y, Chiba K, Tanaka H, Isobe T, Seki M, Kimura S, Makishima H, Nakagawa MM, Kakiuchi N, Kataoka K, Yoshizato T, Nishijima D, Deguchi T, Ohki K, Sato A, Takahashi H, Hashii Y, Tokimasa S, Hara J, Kosaka Y, Kato K, Inukai T, Takita J, Imamura T, Miyano S, Manabe A, Horibe K, Ogawa S, Sanada M. Landscape of driver mutations and their clinical impacts in pediatric B-cell precursor acute lymphoblastic leukemia. Blood Adv. 2020 Oct 27;4(20):5165-5173.

2019

1. Ohki K, Kiyokawa N, Saito Y, Hirabayashi S, Nakabayashi K, Ichikawa H, Momozawa Y, Okamura K, Yoshimi A, Ogata-Kawata H, Sakamoto H, Kato M, Fukushima K, Hasegawa D, Fukushima H, Imai M, Kajiwara R, Koike T, Komori I, Matsui A, Mori M, Moriwaki K, Noguchi Y, Park MJ, Ueda T, Yamamoto S, Matsuda K, Yoshida T, Matsumoto K, Hata K, Kubo M, Matsubara Y, Takahashi H, Fukushima T, Hayashi Y, Koh K, Manabe A, Ohara A. Clinical and molecular characteristics of MEF2D fusion-positive precursor B-cell acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion. Haematologica. 2019 Jan;104(1):128-137.
2. Ikeda J, Shiba N, Tsujimoto SI, Yoshida M, Nakabayashi K, Ogata-Kawata H, Okamura K, Takeuchi M, Osumi T, Tomizawa D, Hata K, Kiyokawa N, Ito S, Kato M. Whole transcriptome sequencing reveals a KMT2A-USP2 fusion in infant acute myeloid leukemia. Genes Chromosomes Cancer. 2019 Sep;58(9):669-672.
3. Osumi T, Watanabe A, Okamura K, Nakabayashi K, Yoshida M, Tsujimoto SI, Uchiyama M, Takahashi H, Tomizawa D, Hata K, Kiyokawa N, Kato M. Acute promyelocytic leukemia with a cryptic insertion of RARA into TBL1XR1. Genes Chromosomes Cancer. 2019 Nov;58(11):820-823.
4. Yoshida M, Nakabayashi K, Ogata-Kawata H, Osumi T, Tsujimoto SI, Shirai R, Yoshida K, Okamura K, Matsumoto K, Kiyokawa N, Tomizawa D, Hata K, Kato M. A novel KMT2A-ACTN2 fusion in infant B-cell acute lymphoblastic leukemia. Pediatr Blood Cancer. 2019 Aug;66(8):e27821.

2018

1. Ueno-Yokohata H, Okita H, Nakasato K, Hishiki T, Shirai R, Tsujimoto S, Osumi T, Yoshimura S, Yamada Y, Shioda Y, Kiyotani C, Terashima K, Miyazaki O, Matsumoto K, Kiyokawa N, Yoshioka T, Kato M. Preoperative diagnosis of clear cell sarcoma of the kidney by detection of BCOR internal tandem duplication in circulating tumor DNA. Genes Chromosomes Cancer. 2018 Oct;57(10):525-529.
2. Tsujimoto S, Osumi T, Uchiyama M, Shirai R, Moriyama T, Nishii R, Yamada Y, Kudo K, Sekiguchi M, Arakawa Y, Yoshida M, Uchiyama T, Terui K, Ito S, Koh K, Takita J, Ito E, Tomizawa D, Manabe A, Kiyokawa N, Yang JJ, Kato M. Diplotype analysis of NUDT15 variants and 6-mercaptopurine sensitivity in pediatric lymphoid neoplasms. Leukemia. 2018 Dec;32(12):2710-2714.
3. Osumi T, Tsujimoto SI, Tamura M, Uchiyama M, Nakabayashi K, Okamura K, Yoshida M, Tomizawa D, Watanabe A, Takahashi H, Hori T, Yamamoto S, Hamamoto K, Migita M, Ogata-Kawata H, Uchiyama T, Kizawa H, Ueno-Yokohata H, Shirai R, Seki M, Ohki K, Takita J, Inukai T, Ogawa S, Kitamura T, Matsumoto K, Hata K, Kiyokawa N, Goyama S, Kato M. Recurrent RARB Translocations in Acute Promyelocytic Leukemia Lacking RARA Translocation. Cancer Res. 2018 Aug 15;78(16):4452-4458.
4. Takahashi H, Kajiwara R, Kato M, Hasegawa D, Tomizawa D, Noguchi Y, Koike K, Toyama D, Yabe H, Kajiwara M, Fujimura J, Sotomatsu M, Ota S, Maeda M, Goto H, Kato Y, Mori T, Inukai T, Shimada H, Fukushima K, Ogawa C, Makimoto A, Fukushima T, Ohki K, Koh K, Kiyokawa N, Manabe A, Ohara A. Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children's Cancer Study Group (TCCSG) Study L04-16. Int J Hematol. 2018 Jul;108(1):98-108.

2017

1. Yaguchi A, Ishibashi T, Terada K, Ueno-Yokohata H, Saito Y, Fujimura J, Shimizu T, Ohki K, Manabe A, Kiyokawa N. EP300-ZNF384 fusion gene product up-regulates GATA3 gene expression and induces hematopoietic stem cell gene expression signature in B-cell precursor acute lymphoblastic leukemia cells. Int J Hematol. 2017 Aug;106(2):269-281.
2. Osumi T, Kato M, Ouchi-Uchiyama M, Tomizawa D, Kataoka K, Fujii Y, Seki M, Takita J, Ogawa S, Uchiyama T, Ohki K, Kiyokawa N. Blastic transformation of juvenile myelomonocytic leukemia caused by the copy number gain of oncogenic KRAS. Pediatr Blood Cancer. 2017 Sep;64(9).
3. Kato M, Ishimaru S, Seki M, Yoshida K, Shiraishi Y, Chiba K, Kakiuchi N, Sato Y, Ueno H, Tanaka H, Inukai T, Tomizawa D, Hasegawa D, Osumi T, Arakawa Y, Aoki T, Okuya M, Kaizu K, Kato K, Taneyama Y, Goto H, Taki T, Takagi M, Sanada M, Koh K, Takita J, Miyano S, Ogawa S, Ohara A, Tsuchida M, Manabe A. Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children. Leukemia. 2017 Mar;31(3):580-584.
4. Hirabayashi S, Ohki K, Nakabayashi K, Ichikawa H, Momozawa Y, Okamura K, Yaguchi A, Terada K, Saito Y, Yoshimi A, Ogata-Kawata H, Sakamoto H, Kato M, Fujimura J, Hino M, Kinoshita A, Kakuda H, Kurosawa H, Kato K, Kajiwara R, Moriwaki K, Morimoto T, Nakamura K, Noguchi Y, Osumi T, Sakashita K, Takita J, Yuza Y, Matsuda K, Yoshida T, Matsumoto K, Hata K, Kubo M, Matsubara Y, Fukushima T, Koh K, Manabe A, Ohara A, Kiyokawa N; Tokyo Children's Cancer Study Group (TCCSG). ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype. Haematologica. 2017 Jan;102(1):118-129.