Identification of D-type cyclin gene abnormalities and development of novel therapeutic strategies in pediatric acute myeloid leukemia
Project/Area Number |
19K16832
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
|
Research Institution | Kyoto University |
Principal Investigator |
|
Project Period (FY) |
2019-04-01 – 2023-03-31
|
Project Status |
Discontinued (Fiscal Year 2022)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | 白血病 / AML / 遺伝子異常 / t(8;21) / CCND2 / CDK4/6 / オートファジー / 急性骨髄性白血病 / アポトーシス / 次世代シークエンス / 遺伝子変異 / CCND |
Outline of Research at the Start |
本研究の目的は、D型サイクリン遺伝子異常を有する小児の急性骨髄性白血病(AML)症例の割合・臨床的特徴や予後を明確にすること、AML細胞におけるD型サイクリン遺伝子異常の果たす役割およびCDK4/6阻害剤の有効性を明らかにすることである。将来的にAML患者の新規治療戦略につながるだけでなく、D型サイクリン遺伝子異常が白血病の遺伝子検査パネルに組み込まれることで治療効果予測にも寄与する可能性がある。
|
Outline of Final Research Achievements |
In this study, genomic analysis of t(8;21) acute myeloid leukemia (AML) patient samples revealed frequent mutations and overexpression of CCND2 gene. Furthermore, we demonstrated that simultaneous inhibition of CDK4/6 and autophagy exerts synergistic anti-tumor effects in vitro/in vivo in t(8;21) AML cell lines and clinical samples.
|
Academic Significance and Societal Importance of the Research Achievements |
本研究ではt(8;21)という染色体上を持つ急性骨髄性白血病(AML)の患者から収集したサンプルを用いて遺伝子異常を調べることで、CCND2という遺伝子に変異や高発現が高頻度にみられることを明らかにした。これはAMLを引き起こすメカニズムの解明につながる成果ある。またCDK4/6とオートファジーを同時に阻害することが、t(8;21)AML細胞に対し有効である可能性を見出した。これはすぐに臨床応用される成果ではないが、将来的にAMLの個別化医療に結び付く可能性のある知見である。
|
Report
(4 results)
Research Products
(55 results)
-
-
-
-
[Journal Article] Droplet digital polymerase chain reaction assay for the detection of the minor clone of KIT D816V in paediatric acute myeloid leukaemia especially showing RUNX1-RUNX1T1 transcripts.2021
Author(s)
Sasaki K, Tsujimoto S, Miyake M, Uchiyama Y, Ikeda J, Yoshitomi M, Shimosato Y, Tokumasu M, Matsuo H, Yoshida K, Ohki K, Kaburagi T, Yamato G, Hara Y, Takeuchi M, Kinoshita A, Tomizawa D, Taga T, Adachi S, Tawa A, Horibe K, Hayashi Y, Matsumoto N, Ito S, Shiba N.
-
Journal Title
British Journal of Haematology
Volume: 194(2)
Issue: 2
Pages: 414-422
DOI
Related Report
Peer Reviewed
-
[Journal Article] Clinical significance of RAS pathway alterations in pediatric acute myeloid leukemia.2021
Author(s)
Kaburagi T, Yamato G, Shiba N, Yoshida K, Hara Y, Tabuchi K, Shiraishi Y,Ohki K, Sotomatsu M, Arakawa H, Matsuo H, Shimada A, Taki T, Kiyokawa N, Tomizawa D, Horibe K, Miyano S, Taga T, Adachi S, Ogawa S, Hayashi Y.
-
Journal Title
Haematologica
Volume: -
Issue: 3
Pages: 583-592
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
[Journal Article] Transcriptome analysis offers a comprehensive illustration of the genetic background of pediatric acute myeloid leukemia2019
Author(s)
Shiba N, Yoshida K, Hara Y, Yamato G, Shiraishi Y, Matsuo H, Okuno Y, Chiba K, Tanaka H, Kaburagi T, Takeuchi M, Ohki K, Sanada M, Okubo J, Tomizawa D, Taki T, Shimada A, Sotomatsu M, Horibe K, Taga T, Adachi S, Tawa A, Miyano S, Ogawa S, Hayashi Y
-
Journal Title
Blood Adv
Volume: 3
Issue: 20
Pages: 3157-3169
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
[Presentation] The importance of RUNX-NFAT axis as a novel therapeutic target for AML and GVHD2021
Author(s)
Tatsuya Masuda, Hirohito Kubota, Kana Furuichi, Naoya Sakuramoto, Asuka Hada, Ayaka Horiuchi, Asami Sasaki, Kanako Takeda, Mizuho Takeda, Hidemasa Matsuo, Masahiro Hirata, Yoichi Imai, Tatsutoshi Nakahata, Junko Takita, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo
Organizer
第83回日本血液学会学術集会
Related Report
-
-
[Presentation] Development of a novel single cell sequencing method from blood smears and pathological specimens2021
Author(s)
Moe Higashitani, Hidemasa Matsuo, Yutarou Harata, Yuri Ito, Aina Inagami, Nana Ito, Norimitsu Uza, Masahiro Shiokawa, Masashi Kanai, Manabu Muto, Souichi Adachi
Organizer
第80回日本癌学会学術総会
Related Report
-
-
-
-
-
-
[Presentation] RUNX-NFAT Axis As a Novel Therapeutic Target for AML and T Cell Immunity.2020
Author(s)
Tatsuya Masuda, Hirohito Kubota, Naoya Sakuramoto, Asuka Hada, Ayaka Horiuchi, Asami Sasaki, Kanako Takeda, Mizuho Takeda, Hidemasa Matsuo, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo
Organizer
62nd ASH Annual Meeting & Exposition
Related Report
Int'l Joint Research
-
-
-
[Presentation] Examination of the importance of RUNX category in EGFR wild-type non-small cell lung cancer.2020
Author(s)
Atsushi Kobayakawa, Kanako Takeda, Tatsuya Masuda, Yohei Yanagida, Natsuno Obi, Naoya Sakuramoto, Asuka Hada, Ayaka Horiuchi, Mizuho Takeda, Asami Sasaki, Hidemasa Matsuo, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo
Organizer
第79回日本癌学会学術総会
Related Report
-
[Presentation] Novel therapeutic strategy for Kras mutated colorectal cancer and PDAC.2020
Author(s)
Natsuno Obi, Mizuho Takeda, Tatsuya Masuda, Yohei Yanagida, Atsushi Kobayakawa, Naoya Sakuramoto, Asuka Hada, Ayaka Horiuchi, Asami Sasaki, Kanako Takeda, Hidemasa Matsuo, Souichi Adachi, Yasuhiko Kamikubo
Organizer
第79回日本癌学会学術総会
Related Report
-
[Presentation] RUNX-NFAT axis as a novel therapeutic target for AML and T cell immunity.2020
Author(s)
Tatsuya Masuda, Hirohito Kubota, Naoya Sakuramoto, Asuka Hada, Ayaka Horiuchi, Asami Sasaki, Kanako Takeda, Mizuho Takeda, Hidemasa Matsuo, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo
Organizer
第79回日本癌学会学術総会
Related Report
-
[Presentation] Multiple regulation of FGFR signaling through CROX (Cluster regulation of RUNX) in DNPC.2020
Author(s)
Yohei Yanagida, Asami Sasaki, Tatsuya Masuda, Natsuno Obi, Atsushi Kobayakawa, Naoya Sakuramoto, Asuka Hada, Ayaka Horiuchi, Mizuho Takeda, Kanako Takeda, Hidemasa Matsuo, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo
Organizer
第79回日本癌学会学術総会
Related Report
-
-
-
-
[Presentation] Coexistence and prognostic significance of EVI1 expression and driver mutations in KMT2A-rearranged acute myeloid leukemia.2019
Author(s)
Hidemasa Matsuo,Kenichi Yoshida,Kana Nakatani,Yasuhiko Kamikubo,Daisuke Tomizawa,Takashi Taga,Nobutaka Kiyokawa,Seishi Ogawa,Manja Meggendorfer,Claudia Haferlach,Souichi Adachi
Organizer
61st ASH Annual Meeting & Exposition
Related Report
Int'l Joint Research
-
[Presentation] Recurrent gene mutations in pediatric AML patients by targeted sequencing ―the JCCG study, JPLSG AML-05―.2019
Author(s)
Taeko Kaburagi,Genki Yamato,Norio Shiba,Kenichi Yoshida,Yusuke Hara,Yuichi Shiraishi,Kentaro Ohki,Manabu Sotomatsu,Hirokazu Arakawa,Hidemasa Matsuo,Akira Shimada,Tomohiko Taki,Nobutaka Kiyokawa,Daisuke Tomizawa,Keizo Horibe,Satoru Miyano,Takashi Taga,Souichi Adachi,Seishi Ogawa,Yasuhide Hayashi
Organizer
61st ASH Annual Meeting & Exposition
Related Report
Int'l Joint Research
-
[Presentation] Clinical Features of Pediatric Acute Myeloid Leukemia with TP53 and CDKN2A/2B Copy Number Alterations.2019
Author(s)
Yusuke Hara,Tomohiko Taki,Genki Yamato,Kenichi Yoshida,Yusuke Shiozawa,Norio Shiba,Taeko Kaburagi,Yuichi Shiraishi,Kentaro Ohki,Machiko Kawamura,Manabu Sotomatsu,Hirokazu Arakawa,Hidemasa Matsuo,...,Souichi Adachi,Yasuhide Hayashi
Organizer
61st ASH Annual Meeting & Exposition
Related Report
Int'l Joint Research
-
[Presentation] Clinical significances of patients with KMT2C and PHF6 mutations in pediatric acute myeloid leukemia.2019
Author(s)
Taeko Kaburagi,Genki Yamato,Norio Shiba,Kenichi Yoshida,Yusuke Hara,Yuichi Shiraishi,Kentaro Ohki,Manabu Sotomatsu,Hirokazu Arakawa,Hidemasa Matsuo,Akira Shimada,Tomohiko Taki,Nobutaka Kiyokawa,Daisuke Tomizawa,Keizo Horibe,Satoru Miyano,Souichi Adachi,Takashi Taga,Seishi Ogawa,Yasuhide Hayashi
Organizer
第61回日本小児血液・がん学会学術集会
Related Report
-
[Presentation] Clinical and molecular characterization of pediatric acute myeloid leukemia with TP53 alterations.2019
Author(s)
Yusuke Hara,Tomohiko Taki,Genki Yamato,Kenichi Yoshida,Norio Shiba,Taeko Kaburagi,Yuichi Shiraishi,Kentaro Ohki,Machiko Kawamura,Manabu Sotomatsu,Hirokazu Arakawa,Hidemasa Matsuo,Akira Shimada,Nobutaka Kiyokawa,Daisuke Tomizawa,Takashi Taga,Keizo Horibe,Satoru Miyano,Seishi Ogawa,Souichi Adachi,Yasuhide Hayashi
Organizer
第61回日本小児血液・がん学会学術集会
Related Report
-
-
[Presentation] Recurrent gene mutations in pediatric AML by targeted sequencing using a 343-gene custom panel.2019
Author(s)
Taeko Kaburagi,Genki Yamato,Norio Shiba,Kenichi Yoshida,Yusuke Hara,Yuichi Shiraishi,Kentaro Ohki,Manabu Sotomatsu,Hirokazu Arakawa,Hidemasa Matsuo,Akira Shimada,Tomohiko Taki,Nobutaka Kiyokawa,Daisuke Tomizawa,Keizo Horibe,Satoru Miyano,Souichi Adachi,Takashi Taga,Seishi Ogawa,Yasuhide Hayashi
Organizer
第81回日本血液学会学術集会
Related Report
-
-
-
-
-
-
-
[Presentation] Apoptotic cell death induced by p300/CBPSurvivin regulation in triple negative breast cancer.2019
Author(s)
割石菜月,田中直,川口展子,沖中えり佳,小林紫乃,佐々木亜沙美,武田瑞穂,武田佳那子,松尾英将,足立壯一,上久保靖彦
Organizer
第78回日本癌学会学術総会
Related Report
-
[Presentation] Induction of cell death in Malignant rhabdoid tumor (MRT) cells through regulating RUNX-Survivin Axis.2019
Author(s)
三上真充,沖中えり佳,大封智雄,金谷卓弥,小林紫乃,服部悦子,松井恭澄,松尾英将,杉山弘,足立壯一,上久保靖彦
Organizer
第78回日本癌学会学術総会
Related Report
-
[Presentation] Identification of RUNX1-NFATc2 axis as a novel target for overcoming drug-resistant APL.2019
Author(s)
立田俊也,古市華菜,増田達哉,窪田博仁,岩井篤,三上真充,服部悦子,松尾英将,杉山弘,足立壯一,上久保靖彦
Organizer
第78回日本癌学会学術総会
Related Report
-
-
-