Establishment of the myeloid leukemic stem cell-targeted therapy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25253069
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyushu University
• Principal Investigator: Akashi Koichi 九州大学, 医学(系)研究科(研究院), 教授 (80380385)
• Co-Investigator(Kenkyū-buntansha): Miyamoto Toshihiro 九州大学, 大学院医学研究院 病態修復内科学, 講師 (70343324) ; Iwasaki Hiromi 九州大学病院, 遺伝子細胞療法部, 准教授 (20403925) ; Takenaka Katsuto 九州大学病院, 遺伝子細胞療法部, 講師 (30301295)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: がん幹細胞 / 白血病幹細胞 / 免疫不全マウス / TIM-3

Outline of Final Research Achievements

In this study, we have identified common machinery for the development and maintenance of myeloid leukemic stem cells; TIM-3/galectin-9 autocrine loop. CD34+CD38-TIM-3+ myeloid leukemic stem cells produce and secrete galectin-9, TIM-3 ligand in an autocrine manner, leading to the constitutive activation of TIM-3 signaling. TIM-3 signaling promotes self-renewal capacity of the malignant stem cells via co-activation of NF-kB and beta-catenin pathways. Thus, signaling molecules downstream of TIM-3 and galectin-9 ligation, as well as surface TIM-3 itself might be good candidates for cancer stem cell-target therapy common to most myeloid malignancies. In addition to the identification of TIM-3/galectin-9 autocrine loop, we established the novel immunodeficient mice lines; BRGS and BRGSK mice. Human normal and malignant hematopoiesis could be efficiently reconstituted in the novel immunodeficient mice.

Free Research Field

血液内科学