Identification of new therapeutic target for MLL rearranged acute myeloid leukemia
Project/Area Number |
23591547
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
IMAMURA Toshihiko 京都府立医科大学, 医学(系)研究科(研究院), 講師 (30444996)
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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 |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | AML / ATRA / LSD1 / H3K4me2 / MLL / C/EBPA / 分化誘導 / LSD1阻害剤 / mTOR阻害剤 / RARA / 急性骨髄性白血病 / レチノイン酸 / MLL遺伝子 / 分化誘導療法 |
Research Abstract |
This study revealed the potential mechanism of high ATRA sensitivity of MLL-AF9-positive AML compared to MLL-AF4-positive AML. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARA gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1 +24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1 (LSD1), which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cell. These findings suggest that the level of H3K4me2 in the RARA gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] All-trans retinoic acid combined with 5-Aza-2'-deoxycitidine induces C/EBPαexpression and growth inhibition in MLL-AF9-positive leukemic cells2012
Author(s)
Fujiki A, Imamura T, Sakamoto K, Kawashima S, Yoshida H, Hirashima Y, Miyachi M, Yagyu S, Nakatani T, Sugita K, Hosoi H.
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Journal Title
Biochem Biophys Res Commun
Volume: 428
Pages: 216-223
Related Report
Peer Reviewed
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[Journal Article] All-trans retinoic acid combined with 5-Aza-2'-deoxycitidine induces C/EBPα expression and growth inhibition in MLL-AF9-positive leukemic cells.2012
Author(s)
Fujiki A, Imamura T, Sakamoto K, Kawashima S, Yoshida H, Hirashima Y, Miyachi M, Yagyu S, Nakatani T, Sugita K, Hosoi H.
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Journal Title
Biochem Biophys Res Commun
Volume: 428
Issue: 2
Pages: 216-223
DOI
Related Report
Peer Reviewed
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[Journal Article] Quantitative RT-PCR analysis of the MOZ-CBP fusion transcript in therapy-related acute myeloid leukemia with t(8;16)(p11;p13).2012
Author(s)
Fujiki A, Imamura T, Furutani A, Hatano W, Asai D, Hirashima Y, Miyachi M, Tamura S, Tsuchiya K, Iehara T, Ishida H, Yoshihara T, Hosoi H.
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Journal Title
J Pediatr Hematol Oncol
Volume: 34
Issue: 5
Pages: 402-405
DOI
Related Report
Peer Reviewed
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[Journal Article] GATA-2 anomaly and clinical phenotype of a sporadic case of lymphedema, dendritic cell, monocyte, B- and NK-cell (DCML) deficiency, and myelodysplasia2012
Author(s)
Ishida H, Imai K, Homma K, Tamura S, Imamura T, Itoh M, Nonoyama S
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Journal Title
Eur J Pediatr
Volume: 171
Issue: 8
Pages: 1273-1276
DOI
Related Report
Peer Reviewed
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[Presentation] IKZF1 deletion is strongly associated with risk of relapse in pediatric B cell precursor ALL with TCF3-PBX1.2012
Author(s)
Asai D, Imamura T, Suenobu S, Moriya Saito A, Hasegawa D, Deguchi T, Hashii Y, Endo M, Hatakeyama N, Kawasaki H, Hori H, Horibe K, Yagi K, Hara J, Oda M, Sato A.
Organizer
54th ASH Annual Meeting and Exposition
Place of Presentation
Atlanta, GA, U.S.A
Related Report
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[Presentation] Early T-cell precursor ALLにおける臨床および生物学的検討.2012
Author(s)
川島幸子, 今村俊彦, 中谷拓也, 平嶋良章, 田村真一, 大曽根眞也, 石田宏之, 森本 哲, 黒田啓史, 日比成美, 今宿晋作, 細井創.
Organizer
第54回日本小児血液・がん学会
Place of Presentation
横浜
Related Report
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[Presentation] IKZF1 deletion is strongly associated with risk of relapse in intermediate risk group in JACLS ALL02 cohort.2011
Author(s)
Asai D, Imamura T, Suenobu S, Hasegawa D, Deguchi T, Hashii Y, Matsumoto K, Kawasaki H, Hori H, Iguchi A, Kosaka Y, Kato K, Horibe K, Yagi K, Hara J, Oda M.
Organizer
53rd ASH Annual Meeting and Exposition
Place of Presentation
San Diego, CA, U.S.A.
Related Report