Analysis on genetic basis of leukemia relapse and therapy resistance
| Project/Area Number |
23249052
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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 |
Hematology
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| Research Institution | Kyoto University (2013)
The University of Tokyo (2011-2012) |
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Principal Investigator |
OGAWA SEISHi 京都大学, 医学(系)研究科(研究院), 教授 (60292900)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥47,970,000 (Direct Cost: ¥36,900,000、Indirect Cost: ¥11,070,000)
Fiscal Year 2013: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2012: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2011: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
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| Keywords | 白血病 / 幹細胞 / リシーケンス / 遺伝子変異 / エピゲノム / 高速シーケンス / 再発 / 難治性白血病 / ゲノム / エクソーム解析 / エピゲノム解析 / 大量並列シーケンス / RNAスプライシング / 治療抵抗性 / 全ゲノム解析 |
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| Research Abstract |
During the past two decades, significant advance has been made in therapeutics of leukemia. However, overall cure rates for many leukemia types have been less than 50%. In this study, to reveal genetic basis for relapsed or therapy-resistant leukemias, we performed comprehensive mutation studies for different types of leukemia, followed by targeted deep sequencing of newly identified as well as common mutational targets, using massively parallel sequencing in large cohorts of leukemias. We identified a number of new mutational targets, including multiple components of the cohesion complex and the RNA splicing machinery as well as SETBP1, DDX41, and DNA repair genes, many of which were associated with poor clinical outcomes. We further demonstrated that information of mutational status of multiple mutational targets could be used for better prediction of the clinical outcome of patients with AML, enabling their stratification for choice of therapeutics.
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] Landscape of genetic lesions in 944 patients with myelodysplastic syndromes.2014
Author(s)
Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G, Schnittger S, Sanada M, Kon A, Alpermann T, Yoshida K, Roller A, Nadarajah N, Shiraishi Y, Shiozawa Y, Chiba K, Tanaka H, Koeffler HP, Klein HU, Dugas M, Aburatani H, Kohlmann A, Miyano S, Haferlach C, Kern W, Ogawa S.
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Journal Title
Leukemia
Volume: 28(2)
Pages: 4241-247
DOI
Related Report
Peer Reviewed
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[Journal Article] A. Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders2013
Author(s)
Muto T, Sashida G, Oshima M, Wendt GR, Mochizuki-Kashio M, Nagata Y, Sanada M, Miyagi S, Saraya A, Kamio A, Nagae G, Nakaseko C, Yokote K, Shimoda K, Koseki H, Suzuki Y, Sugano S, Aburatani H, Ogawa S, Iwama A.
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Journal Title
J Exp Med.
Volume: 210(12)
Pages: 2627-2639
DOI
Related Report
Peer Reviewed
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[Journal Article] Clonal selection in xenografted TAM recapitulates the evolutionary process of myeloid leukemia in Down syndrome2013
Author(s)
Saida, S., K. Watanabe, A. Sato-Otsubo, K. Terui, K. Yoshida, Y. Okuno, T. Toki, R. Wang, Y. Shiraishi, S. Miyano, I. Kato, T. Morishima, H. Fujino, K. Umeda, H. Hiramatsu, S. Adachi, E. Ito, S. Ogawa, M. Ito, T. Nakahata, and T. Heike.
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Journal Title
blood
Volume: 121
Pages: 1-30
DOI
Related Report
Peer Reviewed
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[Journal Article] Novel splicing-factor mutations in juvenile myelomonocytic leukemia2012
Author(s)
Takita J, Yoshida K, Sanada M, Nishimura R, Okubo J, Motomura A, Hiwatari M, Oki K, Igarashi T, Hayashi Y, Ogawa S
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Polycomb-Mediated Loss of miR-31 Activates NIK-Dependent NF-kap paB Pathway in Adult T Cell Leukemia and Other Cancers2011
Author(s)
Yamagishi M, Nakano K, Miyake A, Yamochi T, Kagami Y, Tsutsiuni A, Matsuda Y, Sato-Otsubo A, Muto S, Utsunomiya A, Yamaguchi K, Uchimaru K, Ogawa S, Watanabe T
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Journal Title
Cancer cell
Volume: 21
Pages: 121-135
Related Report
Peer Reviewed
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[Journal Article] Aberrant activation of ALK kinase by a novel truncated form ALK protein in neuroblastoma2011
Author(s)
Okubo J, Takita J, Chen Y, Oki K, Nishimura R, Kato M, Sanada M, Hiwatari M, Hayashi Y, Igarashi T, Ogawa S
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Frequent pathway mutations of splicing machinery in myelodysplasia2011
Author(s)
Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, Shih LY, Haferlach T, Chiba S, Nakauchi H, Miyano S, Ogawa S
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Journal Title
Nature
Volume: 478
Pages: 64-69
Related Report
Peer Reviewed
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[Journal Article] Polycomb-Mediated Loss of miR-31 Activates NIK-Dependent NF-kap paB Pathway in Adult T Cell Leukemia and Other Cancers2011
Author(s)
Yamagishi M, Nakano K, Miyake A, Yamochi T, Kagami Y, Tsutsiuni A, Matsuda Y, Sato-Otsubo A, Muto S, Utsunomiya A, Yamaguchi K, Uchimaru K, Ogawa S, Watanabe T
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Journal Title
Cancer cell.
Volume: 21
Pages: 121-135
Related Report
Peer Reviewed
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[Journal Article] Frequent pathway mutations of splicing machinery in myelodysplasia2011
Author(s)
Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, Shih LY, Haferlach T, Chiba S, Nakauchi H, Miyano S, Ogawa S
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Journal Title
Nature.
Volume: 478
Pages: 64-69
Related Report
Peer Reviewed
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