Development of the new treatment strategy of ATRA-resistant APL using PP2A-FOXO3A activation pathway
| Project/Area Number |
23591407
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAKAKU Tomoiku 順天堂大学, 医学部, 准教授 (20408256)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | FOXO3A / プロテインホスファターゼ2A / 急性前骨髄球性白血病(APL) / 全トランスレチノイン酸(ATRA) / ATRA耐性 / FTY720 / 活性酸素種 / APL / ATRA / sodium selenate / PP2A / FOXO3a / apoptosis |
|---|
| Research Abstract |
Acute promyelotic leukemia (APL) patients usually respond to all-trans retinoic acid (ATRA) treatment, however, some patients are refractory and resistant to ATRA. Therefore, an alternative strategy to treat APL patients is demanded. Here, we showed that FTY720, an immunosuppressive drug, is capable of inducing apoptosis in both ATRA-sensitive and & -resistant APL cells in vitro and regresses tumor mass generated from ATRA-resistant APL cells in vivo. This demonstrates its capability as a potential therapeutic compound in APL treatment. In addition, we have shown that N-acetylcysteine (NAC) rescues FTY720-dependent apoptosis induction in NB4 cells, implying that FTY720 cytotoxic effect to NB4 cells are due at least partly if not all, to a generation of reactive oxygen species (ROS). These observations demonstrate a potential of FTY720 as a therapeutic compound against APL irrespective of whether it is resistant to ATRA.
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] JAK2V617F mutation status and allele burden in classical Ph-negative myeloproliferative neoplasms in Japan2014
Author(s)
EdahiroY, Morishita S, Takahashi K, Hironaka Y, Yahata Y, Sunami Y, Shirane S, Tsutsui M, Noguchi M, Koike M, Imai K, Noda N, Sekiguchi Y, Tsuneda S, Ohsaka A, Araki M, Komatsu N
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Journal Title
Int J Hematol
Volume: 99(5)
Issue: 5
Pages: 625-634
DOI
Related Report
Peer Reviewed
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[Journal Article] JAK2V617F mutation status and allele burden in classical Ph-negative myeloproliferative neoplasms in Japan2014
Author(s)
EdahiroY, Morishita S, Takahashi K, Hironaka Y, Yahata Y, Sunami Y, Shirane S, Tsutsui M, Noguchi M, Koike M, Imai K, Noda N, Sekiguchi Y, Tsuneda S, Ohsaka A, Araki M, Komatsu N
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Journal Title
Int J Hematol
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] APOA-1 is a Novel Marker of Erythroid Cell Maturation from Hematopoietic Stem Cells in Mice and Humans.2011
Author(s)
Inoue T, Sugiyama D, Kurita R, Oikawa T, Kulkeaw K, Kawano H, Miura Y, Okada M, Suehiro Y, Takahashi A, Marumoto T, Inoue H, Komatsu N, Tani K
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Journal Title
Humans. Stem Cell Rev.
Volume: 7
Pages: 43-52
Related Report
Peer Reviewed
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[Patent(Industrial Property Rights)] JAK2遺伝子の変異解析法2010
Inventor(s)
野田 尚宏,関口 勇地,森下 総 司,常田 聡,小松 則夫,蓮沼 彩,桐 戸 敬太
Industrial Property Rights Holder
独立行政法人産業技術総合研究所・早稲田大学・順天堂大学
Industrial Property Rights Type
特許
Patent Publication Number
2012-034580
Acquisition Date
2010-08-03
Related Report
Overseas
