New treatment strategy for myelodysplastic syndromes targeting the interleukin-2 receptor alpha-chain

Research Project

Project/Area Number	25860795
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Hematology
Research Institution	Nippon Medical School
Principal Investigator	Onodera-Kondo Asaka 日本医科大学, 医学部, 助教 (80468769)
Co-Investigator(Renkei-kenkyūsha)	Tamura Hideto 日本医科大学, 医学部, 准教授 (70256949) Ishibashi Mariko 日本医科大学, 大学院医学研究科, ポストドクター (20599047)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	MDS / CD25 / IL2Rα / 骨髄異形成症候群 / 腫瘍免疫 / IL-2Rα / 免疫抑制
Outline of Final Research Achievements	Myelodysplastic syndromes (MDS) are incurable diseases for transplant-ineligible patients. Our results showed that the interleukin-2 receptor alpha-chain (sIL-2Rα, CD25) was expressed on blasts obtained from some patients, and that a high plasma level of soluble IL-2Rα was independently associated with poor prognosis in MDS. There was no difference in degrees of cell apoptosis, cell proliferation, and drug resistance between CD25+ and CD25- cells; MDS blasts. Interestingly, 0.1-6.4% of bone marrow mononuclear cells had the same phenotype as lineage-CD34+CD38- leukemia stem cells (LSCs), and CD25 expression was increased on LSCs compared with that of other blasts in MDS patients. Thus, CD25-targeting therapy might be effective even for cancer stem cells in MDS.