| Project/Area Number |
16K09845
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
Ishikawa Yuchi 名古屋大学, 医学系研究科, 助教 (80721092)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 造血器腫瘍 / 急性骨髄性白血病 / エンドサイトーシス / CALM / トランスフェリンレセプター / AML / 受容体型チロシンキナーゼ / 白血病治療 / 癌 / 血液内科学 |
|---|
| Outline of Final Research Achievements |
Endocytosis is the essential machinery for many cellular processes. One of the endocytic pathways, Clathrin-dependent endocytosis (CDE) is an important mechanism for internalization of Transferrin receptor (TFR1) and other receptors. Since leukemia cells demanded iron for cell proliferation, in this study, we evaluated the efficacy of leukemia therapy targeting CDE and TFR1 endocytosis. TFR1 and CALM, a component of clathrin-coated vesicles, was highly expressed in primary AML cells and there was a correlation between their expression levels. CALM shRNA transduced AML cells showed a proliferative disadvantage compared to shRNA non-transduced cells. Our data indicated that CALM is essential for leukemia cell proliferation by regulating CDE, especially, TFR1 internalization. Since CALM inactivation significantly blocked the leukemia cell proliferation, our findings provide new therapeutic strategies for leukemia treatment.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究により、造血器悪性疾患においてクラスリン依存性エンドサイトーシスおよびその関連分子CALM、トランスフェリンレセプター(TFR1)標的とする治療が有効である可能性が示された。その有効性はTFR1の発現量、CALM等の発現量とは必ずしも一致が認められず、TFR1、クラスリン依存性エンドサイトーシスに依らない細胞内への鉄の取り込み機構の存在も考えられた。一方で、これらエンドサイトーシスを標的とする治療法の有効性に関連する新たなバイオマーカーの存在が示唆され、その全容解明には更なる研究が必要と考えられた。
|
