2010 Fiscal Year Final Research Report
Analysis of leukemogenic mechanism of MLL-AF4 family and development of new therapeutic strategy of MLL-rearranged acute leukemia
| Project/Area Number |
21791000
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
IMAMURA Toshihiko Kyoto Prefectural University of Medicine, 医学研究科, 助教 (30444996)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 小児血液学 |
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| Research Abstract |
Because the prognosis of MLL-AF4-positive acute lymphoblastic leukemia is still extremely poor, understanding of leukemogenic mechanism of MLL-Af4 fusion gene is important for the development of new treatments. We analyzed the leukemogenic mechanism of MLL-AF4 fusion gene using retroviral gene expression system. As a result of myeloid transformation assay, we revealed that MLL-murine Af4 (mAf4) could immortalize murine linenage-depleted bone marrow (Lin-BM) cells. Using a series of hybrid mutants of human AF4/mAf4, we found that amino acids 1026 to 1177 of mAf4 are essential for the leukemogenesis of MLL-mAf4 fusion gene. Overexpression of HoxA9, A10, and Meis1 was confirmed by quantitative RT-PCR analysis of the transduced Lin-BM cells. Chromatin immunoprecipitation (ChIP) assay demonstrated histone H3 lysine79 (H3K79) dimethylation was occurred in promoter regions of HoxA9. Based on these results, we considered that MLL-mAf4 immortalized murine Lin-BM cells by induction of the overexpression of HoxA genes through H3K79 dimethylation in promoter regions of these genes. Our mouse model expressing MLL-mAf4 reproduces well the leukemogenic mechanism of human MLL-AF4-positive leukemias, it is expected to be a good model for the development of new treatments.
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[Journal Article] Comprehensive analyses and characterization of haemophagocytic lymphohistiocytosis in Vietnamese children.2009
Author(s)
My LT, Lien LB, Hsieh WC, Imamura T, Anh TN, Anh PN, Hung NT, Tseng FC, Chi CY, Dao NT, Le DT, Thinh LQ, Tung TT, Imashuku S, Thuong TC, Su IJ.
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Journal Title
Br J Haematol 148(2)
Pages: 301-310
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[Journal Article] 当院で経験した血液培養陽性の小児がん患者からの考察2009
Author(s)
勝見良樹, 家原知子, 菊地顕, 宮地充, 平嶋良章, 中谷拓也, 柳生茂希, 清水智子, 土屋邦彦, 今村俊彦, 森本哲, 藤田直久, 細井創
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Journal Title
小児がん 46(3)
Pages: 317-323
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[Presentation] Specific MLL fusion partners affect the sensitivity of human and murine leukemic cell lines to demethylating agents.2010
Author(s)
Fujiki A, Imamura T, Yoshida H, Hirashima Y, Miyachi M, Yagyu S, Sugita K, Hosoi H
Organizer
American Society of Hematology, 52nd Annual Meeting
Place of Presentation
Orlando, Florida, U.S.A.
Year and Date
20101204-20101207
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[Presentation] RAD001, an inhibitor of mTOR, enhances monocytic differentiation induced by ATRA through phosphorylation of C/EBPain AML cell lines.2010
Author(s)
Yoshida H, Imamura T, Fujiki A, Hirashima Y, Miyachi M, Sugita K, Hosoi H
Organizer
American Society of Hematology, 52nd Annual Meeting
Place of Presentation
Orlando, Florida, U.S.A.
Year and Date
20101204-20101207
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[Presentation] JACLS ALL-02研究におけるstandard risk群の予後因子解析2010
Author(s)
高橋良博, 今村俊彦, 宇佐美郁哉, 小阪嘉之, 加藤剛二, 河崎裕英, 八木啓子, 堀部敬三, 堀浩樹, 原純一, 小田慈, 中畑龍俊, 工藤亨
Organizer
第52回日本小児血液学会
Place of Presentation
大阪
Year and Date
2010-12-18
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[Presentation] L-asparaginase-induced steatohepatitis in pediatric acute lymphoblastic leukemia.2010
Author(s)
Imamura T, Hashii Y, Tokimasa S, Kobayashi R, Kawasaki H, Hori H, Yagi K, Hara J, Horibe K, Kudo T, Oda M
Organizer
第72回日本血液学会
Place of Presentation
横浜
Year and Date
2010-09-26
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[Presentation] Monocytic di fferentiation of myeloid leukemia cell lines induced by ATRA and 5-Aza-2'-Deoxycitidine.2009
Author(s)
Fujiki A, Imamura T, Hirashima Y, Miyachi M, Yagyu S, Nakatani T, Sugita K, Hosoi H
Organizer
American Society of Hematology, 51st Annual Meeting.
Place of Presentation
New Orleans, Louisiana, U.S.A.
Year and Date
20091205-20091208
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[Presentation] Bisphosphonate therapy for children with Langerhans cell histiocytotsis : A Nationwide survey in Japan.2009
Author(s)
Morimoto A, Shioda Y, Imamura T, Kanegane H, Sato T, Kudo K, Nakagawa S, Nakadate N, Tauchi H, Nagatoshi Y, Kinoshita A, Miyaji R, Asano T, Yabe M, Kamizono J
Organizer
25th Annual Meeting of the Histiocyte Society.
Place of Presentation
Bilbao, Spain.
Year and Date
20090915-20090917
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[Presentation] 難治性慢性血小板減少症に対しRituximab投与を行った3例2009
Author(s)
柴田真弓, 今村俊彦, 吉田路子, 波多野わか, 古谷明代, 戸澤雄紀, 矢野未央, 平嶋良章, 千代延友裕, 石井るみ子, 貫名貞之, 森本哲, 細井創
Organizer
第51回日本小児血液学会
Place of Presentation
東京
Year and Date
2009-11-28
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[Presentation] 抜歯後の止血困難を契機に診断された後天性血友病Aの1女児例2009
Author(s)
東道公人, 藤本一途, 幸道和樹, 山本茜, 大前禎毅, 長村敏生, 猪田浩理, 杉本充彦, 嶋緑倫, 清沢伸幸, 今村俊彦
Organizer
第51回日本小児血液学会
Place of Presentation
東京
Year and Date
2009-11-28
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[Presentation] 当院における急性リンパ性白血病中枢神経系単独再発例のまとめ2009
Author(s)
藤木敦, 今村俊彦, 吉田秀樹, 平嶋良章, 田村真一, 大曽根眞也, 石田宏之, 吉原隆夫, 黒田啓史, 森本哲, 日比成美, 東道伸二郎, 今宿晋作, 細井創
Organizer
第51回日本小児血液学会
Place of Presentation
東京
Year and Date
2009-11-27
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[Presentation] 当科における急性骨髄性白血病の治療成績について2009
Author(s)
吉田秀樹, 今村俊彦, 藤木敦, 平嶋良章, 中谷拓也, 石田宏之, 森本哲, 吉原隆夫, 黒田啓史, 日比成美, 東道伸二郎, 今宿晋作, 細井創
Organizer
第4回京都地区小児血液腫瘍研究会
Place of Presentation
京都
Year and Date
2009-07-25
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