Integrative analysis of DNA and RNA structural analysis in refractory leukemia in children

• Project/Area Number: 26713037
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Pediatrics
• Research Institution: National Center for Child Health and Development (2015-2016); The University of Tokyo (2014)
• Principal Investigator: Kato Motohiro 国立研究開発法人国立成育医療研究センター, 小児血液・腫瘍研究部, 医長 (40708690)
• Co-Investigator(Renkei-kenkyūsha): Ogawa Seishi 京都大学, 腫瘍生物学, 教授 (60292900) ; TAKITA Junko 東京大学, 小児科, 准教授 (00359621)
• Research Collaborator: SEKI Masafumi
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000); Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2014: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: 癌 / 小児白血病 / 分子遺伝学 / ゲノム解析

Outline of Final Research Achievements

We investigated molecular biology underlying development of pediatric leukemia, through whole exome sequencing and whole transcriptome sequencing.
In acute lymphoblastic leukemia in children, using intron capture analysis, we identified translocations which predicted clinical outcome under short maintenance therapy, which could contribute to optimization of therapy duration. Furthermore, we reported mechanisms in false-negative in FISH analysis for NUP214-ABL1 fusion in refractory leukemia, and we also reported that duplication of mutant KRAS by gain of chromocome 12 caused blastic crisis of Juvenile myelomonocytic leukemia. Additionally, via transcriptome sequencing, we identified a novel fusion including SPI1, a transcription factor, in pediatric T-cell acute lymphoblastic leukemia.

Research Products

• [Int'l Joint Research] St. Jude小児病院(米国)
• [Int'l Joint Research] Sheffield Children’s Hospital(英国)
• [Int'l Joint Research] St. Jude Children's Research Hospital(米国)
• [Journal Article] Long-term outcome of six-month maintenance chemotherapy for acute lymphoblastic leukemia in children. (2017)
  • Author(s): 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.
  • Journal Title: Leukemia. Volume: 31 Issue: 3 Pages: 580-584
  • DOI: 10.1038/leu.2016.274
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genomic analysis of clonal origin of Langerhans cell histiocytosis following acute lymphoblastic leukemia (2015)
  • Author(s): 2.Kato M, Seki M, Yoshida K, Sato Y, Oyama R, Arakawa Y, Kishimoto H, Taki T, Akiyama M, Shiraishi Y, Chiba K, Tanaka H, Mitsuiki N, Kajiwara M, Mizutani S, Sanada M, Miyano S, Ogawa S, Koh K, Takita J.
  • Journal Title: British Journal of Haematology Volume: Nov 5 Issue: 1 Pages: 169-172
  • DOI: 10.1111/bjh.13841
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Duration of maintenance therapy: long-term outcome of TCCSG L92-13 (2016)
  • Author(s): Kato M, Koh K, Manabe A
  • Organizer: The 27th International BFM meeting
  • Place of Presentation: アテネ
  • Year and Date: 2016-04-22
  • Int'l Joint Research / Invited
• [Presentation] TAL1 and MYB abnormalities in childhood T-cell acute lymphoblastic leukemia (2015)
  • Author(s): Masafumi Seki, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Motohiro Kato, Shunsuke Kimura, Katsuyoshi Koh, Ryoji Hanada, Satoru Miyano, Toshihiko Imamura, Keizo Horibe, Nobutaka Kiyokawa, Atsushi Manabe, Akira Ohara, Yasuhide Hayashi, Akira Oka, Seishi Ogawa, Junko Takita
  • Organizer: The 57th annual meeting of the American Society of Hematology
  • Place of Presentation: Orlando
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] Whole exome and transcriptome analyses in pediatric T-cell acute lymphoblastic leukemia (2014)
  • Author(s): 関正史
  • Organizer: 第57回米国血液学会
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2014-12-06 – 2014-12-09