Establishment of new targeted therapy against acute blastic transformation of chronic myeloid leukemia
| Project/Area Number |
24790962
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TOMOHIKO Sato 東京大学, 医学部附属病院, 助教 (90553694)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 白血病幹細胞 |
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| Research Abstract |
Introduction of CML into Evi1-IRES-GFP knock-in mice, a versatile HSC-reporter strain, enables us to separate Evi1-high CML cells from the individual. Evi1-IRES-GFP allele models of CML in chronic phase (CML-CP) revealed that Evi1 is predominantly enriched in the stem cell fraction and associated with an enhanced proliferative as well as a leukemia-initiating capacity and that Evi1-high CML-CP cells exhibit resistance to TKIs. Overexpressing BCR-ABL and NUP98-HOXA9 in Evi1-IRES-GFP knock-in mice to model CML in blast crisis (CML-BC), in which Evi1-high cells turned to be a major population as opposed to a minor population in CML-CP models, showed that Evi1-high CML-BC cells have a greater potential to recapitulate the disease and appear resistant to TKIs. Given that Evi1 heterozygosity ameliorates CML-CP and CML-BC development and that the combination of Evi1 and BCR-ABL causes acute myeloid leukemia resembling CML-BC, Evi1 could regulate CML development as a potent driver.
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] Evi1 defines leukemia-initiating capacity and tyrosine kinase inhibitor resistance in chronic myeloid leukemia.2014
Author(s)
Sato T, Goyama S, Kataoka K, Nasu R, Tsuruta-Kishino T, Kagoya Y, Nukina A, Kumagai K, Kubota N, Nakagawa M, Arai S, Yoshimi A, Honda H, Kadowaki T, Kurokawa M.
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Journal Title
Oncogene
Volume: 33
Issue: 42
Pages: 5028-5038
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Evi1 Defines Leukemia-initiating Capacity and Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia2014
Author(s)
Tomohiko Sato, Susumu Goyama, Keisuke Kataoka, Ryo Nasu, Takako Tsuruta-Kishino, Yuki Kagoya, Arika Nukina, Katsuyoshi Kumagai, Naoto Kubota, Masahiro Nakagawa, Shunya Arai, Akihide Yoshimi, Hiroaki Honda, Takashi Kadowaki and Mineo Kurokawa
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Journal Title
Related Report
Peer Reviewed
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[Presentation] Evi1 Defines Leukemia-initiating Capacity and Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia2014
Author(s)
Tomohiko Sato, Susumu Goyama, Keisuke Kataoka, Ryo Nasu, Takako Tsuruta-Kishino, Yuki Kagoya, Arika Nukina, Katsuyoshi Kumagai, Naoto Kubota, Masahiro Nakagawa, Shunya Arai, Akihide Yoshimi, Hiroaki Honda, Takashi Kadowaki and Mineo Kurokawa
Organizer
AACR 2014 annual meeting
Place of Presentation
San Diego, CA, USA
Related Report
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