Analysis of ligand dependent resistance mechanism of RTK inhibitors
Project/Area Number |
24591387
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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 |
Hematology
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Research Institution | Nagoya University |
Principal Investigator |
KIYOI Hitoshi 名古屋大学, 医学(系)研究科(研究院), 教授 (90314004)
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Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 血液腫瘍学 / チロシンキナーゼ / 分子標的療法 / 白血病 / 耐性機構 |
Outline of Final Research Achievements |
In this study, I analyzed the FLT3 ligand (FL)-dependent resistance mechanism of FLT3 inhibitors using wild type FLT3 (Wt-FLT3) and FLT3-ITD or extracellular domain-lacked FLT3-ITD (cyFLT3-ITD) co-expressing cells. I demonstrated that FL-stimulation activates co-expressing-Wt-FLT3 and MAPK, resulting in the reduction of anti-leukemia activity of FLT3 inhibitor. This FL-dependent inhibitory effect of FLT3 inhibitors was also confirmed in the human leukemia cell xenotransplant mouse models, in which Wt-FLT3 and FLT3-ITD co-expressing leukemia cells were not sufficiently eradicated by FLT3 inhibitors. These results also indicate that Wt-FLT3 expression level is a molecular marker for predicting the efficacy of FLT3 inhibitors.
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Expression of CD56 is an unfavorable prognostic factor for acute promyelocytic leukemia with higher initial white blood cell counts.2014
Author(s)
Ono T, Takeshita A, Kishimoto Y, Kiyoi H, Okada M, Yamauchi T, Emi N, Horikawa K, Matsuda M, Shinagawa K, Monma F, Ohtake S, Nakaseko C, Takahashi M, Kimura Y, Iwanaga M, Asou N, Naoe T; Japan Adult Leukemia Study Group.
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Journal Title
Cancer Sci
Volume: 105
Issue: 1
Pages: 97-104
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] De novo diffuse large B-cell lymphoma with a CD20 immunohistochemistry-positive and flow cytometry-negative phenotype: Molecular mechanisms and correlation with rituximab sensitivity.2014
Author(s)
Tokunaga T, Tomita A, Sugimoto K, Shimada K, Iriyama C, Hirose T, Shirahata-Adachi M, Suzuki Y, Mizuno H, Kiyoi H, Asano N, Nakamura S, Kinoshita T, Naoe T.
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Journal Title
Cancer Sci.
Volume: 105
Issue: 1
Pages: 35-43
DOI
Related Report
Peer Reviewed
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[Journal Article] Leukemic evolution of donor-derived cells harboring IDH2 and DNMT3A mutations after allogeneic stem cell transplantation.2014
Author(s)
Yasuda T, Ueno T, Fukumura K, Yamato A, Ando M, Yamaguchi H, Soda M, Kawazu M, Sai E, Yamashita Y, Murata M, Kiyoi H, Naoe T, Mano H.
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Journal Title
Leukemia
Volume: 28
Issue: 2
Pages: 426-428
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Role of hematopoietic stem cell transplantation for relapsed acute promyelocytic leukemia: a retrospective analysis of JALSG-APL97.2013
Author(s)
Fujita H, Asou N, Iwanaga M, Hyo R, Nomura S, Kiyoi H, Okada M, Inaguma Y, Matsuda M, Yamauchi T, Ohtake S, Izumi T, Nakaseko C, Ishigatsubo Y, Shinagawa K, Takeshita A, Miyazaki Y, Ohnishi K, Miyawaki S, Naoe T; Japan Adult Leukemia Study Group.
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Journal Title
Cancer Sci
Volume: 104
Issue: 10
Pages: 1339-1345
DOI
Related Report
Peer Reviewed
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[Journal Article] The demarcation between younger and older acute myeloid leukemia patients.2013
Author(s)
Yanada M, Ohtake S, Miyawaki S, Sakamaki H, Sakura T, Maeda T, Miyamura K, Asou N, Oh I, Miyatake J, Kanbayashi H, Takeuchi J, Takahashi M, Dobashi N, Kiyoi H, Miyazaki Y, Emi N, Kobayashi Y, Ohno R, Naoe T.
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Journal Title
Cancer
Volume: 119
Issue: 18
Pages: 3326-3333
DOI
Related Report
Peer Reviewed
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[Journal Article] Long-term outcome and prognostic factors of elderly patients with acute promyelocytic leukemia2012
Author(s)
Ono T, Takeshita A, Kishimoto Y, Kiyoi H, Okada M, Yamauchi T, Tsuzuki M, Horikawa K, Matsuda M, Shinagawa K, Monma F, Ohtake S, Nakaseko C, Takahashi M, Kimura Y, Iwanaga M, Asou N, Naoe T
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Journal Title
Cancer Sci.
Volume: 103
Issue: 11
Pages: 174-1978
DOI
Related Report
Peer Reviewed
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[Journal Article] Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia2012
Author(s)
Doisaki S, Muramatsu H, Shimada A, Takahashi Y, Mori-Ezaki M, Sato M, Kawaguchi H, Kinoshita A, Sotomatsu M, Hayashi Y, Furukawa-Hibi Y, Yamada K, Hoshino H, Kiyoi H, Yoshida N, Sakaguchi H, Narita A, Wang X, Ismael O, Xu Y, Nishio N, Tanaka M, Hama A, Koike K, Kojima S
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Journal Title
Blood
Volume: 120
Issue: 7
Pages: 1485-1488
DOI
Related Report
Peer Reviewed
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