The mechanism of autocrine and paracrine growth promotion of CML cells
Project/Area Number |
25860792
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Hematology
|
Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
SUGITANI Mio 京都府立医科大学, 医学部附属病院, 研究員 (60648749)
|
Co-Investigator(Kenkyū-buntansha) |
TANIWAKI Masafumi 京都府立医科大学, 医学部附属病院, 教授 (80163640)
KURODA Junya 京都府立医科大学, 医学部附属病院, 講師 (70433258)
|
Project Period (FY) |
2013-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 慢性骨髄性白血病 / Galectin-3 / 骨髄腫瘍環境由来治療抵抗性 / オートクライン・パラクライン / 幹細胞能 |
Outline of Final Research Achievements |
Tyrosin kinase inhibitors(TKIs) for BCR-ABL have dramatically improved the outcome of chronic myelogenous leukemia(CML). However, the complete elimination of CML clones has been rarely achieved by TKIs due to a variety of protective mechanisms. One reason for TKI resistance is the bone marrow microenvironment(BMME)-mediated drug resistance. We found that BMME-induced galectin-3(Gal-3) in CML plays an important role in drug resistance in previous study. Furthermore, we in this study disclosed the results as follows. ①The bovine SERPINA1-fetal bovine serum albumin complex was specifically suppressed in conditioned medium from Gal-3-overexpressing cells. Suppression of SERPINA1-albumin complex by Gal-3 overexpression led to paracrine growth promotion of CML cells. ②The combination of TKI and PP2A activator FTY720 could overcome Gal-3-mediated drug resistance to TKI. ③ALDH1 known as the marker of cancer stem cell and drug resistance was induced by Gal-3 overexpression in CML cells.
|
Report
(3 results)
Research Products
(6 results)
-
[Journal Article] Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.2014
Author(s)
Chinen Y, Kuroda J, Shimura Y, Nagoshi H, Kiyota M, Yamamoto-Sugitani M, Mizutani S, Sakamoto N, Ri M, Kawata E, Kobayashi T, Matsumoto Y, Horiike S, Iida S, Taniwaki M.
-
Journal Title
Cancer Res
Volume: 74
Issue: 24
Pages: 7418-7429
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] 8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia.2014
Author(s)
Chinen Y, Sakamoto N, Nagoshi H, Taki T, Maegawa S, Tatekawa S, Tsukamoto T, Mizutani S, Shimura Y, Yamamoto-Sugitani M, Kobayashi T, Matsumoto Y, Horiike S, Kuroda J, Taniwaki M.
-
Journal Title
J Hematol Oncol
Volume: 7
Issue: 1
Pages: 68-68
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
[Journal Article] Suppression of SERPINA1-albumin complex formation by galectin-3 overexpression leads to paracrine growth promotion of chronic myelogenous leukemia cells.2014
Author(s)
Nakayama R, Kuroda J, Taniyama N, Yamamoto-Sugitani M, Wada S, Kiyota M, Mizutani S, Chinen Y, Matsumoto Y, Nagoshi H, Shimura Y, Kobayashi T, Horiike S, Sato K, Taniwaki M.
-
Journal Title
Leukemia Research
Volume: 38
Issue: 1
Pages: 103-108
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] FTY720 induces apoptosis of chronic myelogenous leukemia cells via dual activation of BIM and BID and overcomes various types of resistance to tyrosine kinase inhibitors.2013
Author(s)
Kiyota M, Kuroda J, Yamamoto-Sugitani M, Shimura Y, Nakayama R, Nagoshi H, Mizutani S, Chinen Y, Sasaki N, Sakamoto N, Kobayashi T, Matsumoto Y, Horiike S, Taniwaki M.
-
Journal Title
Apoptosis
Volume: 18
Issue: 11
Pages: 366-374
DOI
Related Report
Peer Reviewed
-
[Presentation] Phosphoinositide-dependent protein kinase 1 is a crucial cell signaling mediator in multiple myeloma2014
Author(s)
Chinen Y, Kuroda J, Shimura Y, Nagoshi H, Kiyota M, Sugitani M, Mizutani S, Sakamoto N, Ri M, Kawata E, Kobayashi T, Matsumoto Y, Horiike S, Iida S, Taniwaki M.
Organizer
第76回日本血液学会学術集会
Place of Presentation
大阪国際会議場
Year and Date
2014-11-01
Related Report
-
[Presentation] PVT-1-NSMCE2 fusion gene enhances BCL-XL expression and drug resistance in leukemic cells.2014
Author(s)
Chinen Y, Sakamoto N, Nagoshi H, Taki T, Kobayashi S, Nishida K, Maegawa S, Kiyota M, Mizutani S, Shimura Y, Sugitani M, Kobayashi T, Matsumoto Y, Horiike S, Kuroda J, Taniwaki M.
Organizer
第76回日本血液学会学術集会
Place of Presentation
大阪国際会議場
Year and Date
2014-10-31
Related Report