Development of new strategy for MDS treatment targeting CXCL12 signaling

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670186
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Kobe University (2016); Tokyo Medical and Dental University (2014-2015)
• Principal Investigator: Abe Shiho 神戸大学, 医学部附属病院, 特命助教 (30632111)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 造血幹細胞ニッチ / 骨髄異形成症候群 / CXCL12 / アポトーシス

Outline of Final Research Achievements

We analyzed the association between the CXCL12(+) stromal cells and CD34(+) tumor cells of myelodysplastic syndromes (MDS). In MDS bone marrow, CXCL12(+) cell density was higher than control bone marrow. The CXCL12(+) cells were in contact with CD34(+) tumor cells, which were positive for several anti-apoptotic markers. Furthermore, CXCL12-high MDS cases had the greater tendency to show rapid disease progression than CXCL12-low cases. In vitro analysis, MDS-derived hematopoietic cell line cells cocultured with CXCL12(+) stromal cell line cells showed upregulation of anti-apoptotic molecules and drug-resistance for Ara-C treatment. These phenomena were inhibited by CXCR4 antagonist, AMD3100, therefore CXCL12-CXCR4 signaling was essential for the interaction between MDS cells and CXCL12(+) stromal cells. Thus, CXCL12(+) stromal cells may represent a novel MDS therapeutic target.

Free Research Field

骨髄病理