Hypoxia attenuates growth of MPN cells through suppression of SHP-2 expression and subsequent inhibition of JAK2V617F activity
| Project/Area Number |
21591197
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | University of Yamanashi |
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Principal Investigator |
KIRITO Keita 山梨大学, 大学院・医学工学総合研究部, 教授 (90306150)
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| Co-Investigator(Kenkyū-buntansha) |
KOMATSU Norio 順天堂大学, 医学部, 教授 (50186798)
SAKOE Kumi 自治医科大学, 医学部, 研究員 (10398505)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 骨髄増殖性腫瘍 / JAK2V617F / SHP-2 / 低酸素環境 / JAK2変異 / 造血幹細胞 / 骨髄増殖性疾患 / 低酸素 / JAK2 / HIF-1 |
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| Research Abstract |
We found that hypoxia suppressed activity of JAK2V617F and induced growth arrest in JAK2V617F-positive MPN cells. SHP-2 plays important roles in these process. Interestingly, several studies have reported that SHP-2 is required for the activation of JAK2 by cytokines. In addition, recent studies have revealed that the activity of SHP-2 is increased in platelets from MPN patients. In conclusion, hypoxic environment may modulate fate of JAK2-positive MPN cells through suppression of SHP-2 levels and subsequent suppression of JAK2V617F activity.
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Report
(4 results)
Research Products
(43 results)
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[Journal Article] Romiplostim for the treatment ofchronic immune thrombocytopenia inadult Japanese patients : a double-blind, randomized Phase iii clinicaltrial2011
Author(s)
Shirasugi Y, Ando K, Miyazaki K, Tomiyama Y, Okamoto S, Kurokawa M, Kirito K, Yonemura Y, Mori S, Usuki K, Iwato K, Hashino S, Wei H, Lizambri R
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Journal Title
International Journal of Hematology
Related Report
Peer Reviewed
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[Journal Article] Inhibition of hypoxia-inducible factor-1 function enhances the sensitivity of multiple myelomacells to melphalan2009
Author(s)
Hu Y, Kirito K, Yoshida K, MitsumoriT, Nakajima K, Nozaki Y, Hamanaka S, Nagashima T, Kunitama M, Sakoe K, Komatsu N
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Journal Title
Molecular cancer therapeutics
Volume: 8
Pages: 2329-2338
Related Report
Peer Reviewed
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[Presentation] MPNの分類と病態2011
Author(s)
桐戸敬太
Organizer
第73回日本血液学会総会
Place of Presentation
名古屋国際会議場(愛知県)(招待講演)
Year and Date
2011-10-16
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