2013 Fiscal Year Final Research Report
Molecular basis of myeloid leukemogenesis
| Project/Area Number |
23240125
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Carcinogenesis
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
NAKAMURA Takuro 公益財団法人がん研究会, がん研究所発がん研究部, 部長 (00180373)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Takashi 公益財団法人がん研究会, がん研究所発がん研究部, 研究員 (00535833)
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| Co-Investigator(Renkei-kenkyūsha) |
GOITSUKA Ryo 東京理科大学, 生命科学研究所, 教授 (50301552)
ITO Etsuro 弘前大学, 大学院医学系研究科, 教授 (20168339)
HAYASHI Yasuhide 群馬県小児医療センター, センター長 (30238133)
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| Project Period (FY) |
2011-11-18 – 2014-03-31
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| Keywords | 骨髄性白血病 / 実験動物モデル / 遺伝子経路 / 転写制御 / シグナリング |
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| Research Abstract |
We have analyzed the molecular network around Hoxa9 and Meis1 that play a important role as transcription factors in development of acute myeloid leukemia (AML). Meis1 is required for engraftment of leukemic cells in bone marrow niche. ChIP-Seq analysis and gene expression profiling identified the Meis1 target gene Sytl1 that is responsible for Meis1's function. Sytl1 facilitates intracellular trafficking of membrane-bound receptors to modulate cell-cell interaction between leukemic cells and bone marrow stroma. Trib1 downregulates the C/EBPa protein and regulates granulocytic differentiation. Trib1 somatic mutation was identified in a case of human AML. Retroviral tagging experiments identified Bcl11a as a novel cooperative gene for Trib1 in leukemogenesis.
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Research Products
(36 results)
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[Journal Article] Homeodomain transcription factor Meis1 is a critical regulator of adult bone marrow hematopoiesis2014
Author(s)
Ariki R, Morikawa S, Mabuchi Y, Suzuki S, Nakatake M, Yoshioka K, Hidano S, Nakauchi H, Matsuzaki Y, Nakamura T, Goitsuka R
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Journal Title
PLOS One
Volume: 9
Pages: e87646
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[Journal Article] Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia2013
Author(s)
Kon S, Minegishi N, Tanabe K, Watanabe T, Funaki T. Wong WF, Sakamoto D, Higuchi Y, Kiyonari H, Asano K, Iwakura Y, Fukumoto M, Osato M, Sanada M, Ogawa S, Nakamura T, Satake M
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Journal Title
J Clin Invest
Volume: 123
Pages: 1123-1137
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[Journal Article] Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 72013
Author(s)
Nagamachi A, Matsui H, Asou H, Ozaki Y, Aki D, Kanai A, Takubo K, Suda T, Nakamura T, Wolff L, Honda H, Inaba T
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Journal Title
Cancer Cell
Volume: 24
Pages: 305-317
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[Journal Article] Identification of TRIB1 R107L gain-of-function mutation in human acute megakaryocytic leukemia2012
Author(s)
Yokoyama T, Toki T, Aoki Y, Kanezaki R, Park M, Kanno Y, Takahara T, Yamazaki Y, Ito E, Hayashi Y, Nakamura T
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Journal Title
Blood
Volume: 199
Pages: 2608-2611
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[Journal Article] MLV integration induces the formation of transcription factor complexes on palindromic sequences in the Stat5a gene during the development of pre-B lymphomagenesis2011
Author(s)
Tsuruyama T, Hiratsuka T, Jin G, Imai Y, Takeuchi H, Maruyama Y, Kanaya K, Ozeki M, Takakuwa T, Haga H, Tamaki K, Nakamura T
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Journal Title
Am J Pathol
Volume: 178
Pages: 1374-1386
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[Journal Article] RNA export factor RAE1 contributes to NUP98-HOXA9-mediated leukemogenesis2011
Author(s)
Funasaka T, Nakano H, Wu Y, Hashizume C, Gu L, Nakamura T, Wang W, Zhou P, Moore MAS, Sato H, Wong RW
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Journal Title
Cell Cycle
Volume: 10
Pages: 1456-1467
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