Establishment of a novel therapeutic strategy for leukemia by targeting the hematopoietic stem cell niche.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390248
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Tokai University
• Principal Investigator: ANDO Kiyoshi 東海大学, 医学部, 教授 (70176014)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 白血病幹細胞 / 白血病ニッチ / PAI-1

Outline of Final Research Achievements

We have reported that plasminogen activator inhibitor-1 (PAI-1), a negative regulator of the fibrinolytic pathway, expressed in the BM niche and negatively regulated the hematopoietic regeneration in the BM microenvironment. Pharmacological inhibition of PAI-1 activity significantly improved hematopoietic recovery after hematopoietic stem cell transplantation. In this study, we demonstrated several evidences about the relationship leukemia and PAI-1. First, leukemia stem cells highly expressed the PAI-1. Second, PAI-1-expressinng leukemia showed resistance to anti-tumor therapy. Finally, co-administration of leukemia-specific molecular target drug and PAI-1 inhibitor facilitated anti-tumor effects. Our results indicate that the inhibition of PAI-1 activity could be a therapeutic approach to eliminate the therapy-resistant leukemia stem cells.

Free Research Field

血液腫瘍内科学