Characterization of ROCK and new therapeutic strategy for extramedullary leukemia

2014 Fiscal Year Final Research Report

• Project/Area Number: 24791064
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Shimane University
• Principal Investigator: ONISHI CHIE 島根大学, 医学部, 医科医員 (30598115)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 急性骨髄性白血病 / ITD-Flt３変異 / 細胞遊走 / ROCK

Outline of Final Research Achievements

ITD-Flt3 enhance cell migration toward the chemokine CXCL12/SDF1. A comparison of the CXCL12-induced gene expression between ITD-Flt3+ and ITD-Flt3- Ba/F3 cells revealed that one of the genes that was differentially regulated by CXCL12 depending on the Flt3 status was Rock1. The expression of Rock1 in the ITD-Flt3+ cells that migrated toward CXCL12 was significantly higher than in ITD-Flt3- cells that migrated toward CXCL12. In ITD-Flt3- cells, Rock1 expression and MYPT1 phosphorylation were transiently up-regulated but were subsequently down-regulated by CXCL12. In contrast, the presence of ITD-Flt3 blocked the CXCL12-induced down-regulation of Rock1 and early MYPT1 dephosphorylation. Rock1 antagonists or Rock1 shRNA abolished the enhanced migration of ITD-Flt3+ cells toward CXCL12. Our findings demonstrate that ITD-Flt3 increases cell migration toward CXCL12 by antagonizing the down-regulation of Rock1 expression.

Free Research Field

血液病学