Uncover molecular basis on cancer microenvironment regulating leukemia stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15209
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kyoto University
• Principal Investigator: TANAKA HIROKI 京都大学, 医学研究科, 特定助教 (20725452)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 間葉系幹細胞 / T細胞

Outline of Final Research Achievements

Chronic myelogenous leukemia (CML) caused by hematopoietic stem cells expressing the Bcr-Abl fusion gene. We found that Sipa1 deficient mice reject CML cells expressing Bcr-Abl, which cause lethal CML disease in wild-type mice. Resistance requires both T cells and nonhematopoietic cells. Sipa1　deficient mesenchymal stroma cells (MSCs) show enhanced activation and directed migration to Bcr-Abl expressing cells in tumor tissue and preferentially produce Cxcl9, which in turn recruits Sipa1 deficient memory T cells that have markedly augmented chemotactic activity. Sipa1 deficiency uncovers a host immune mechanism potentially capable of eradicating Bcr-Abl expressing cells via coordinated interplay between MSCs and immune T cells.

Free Research Field

腫瘍学、免疫学

Academic Significance and Societal Importance of the Research Achievements

我々が明らかにした慢性骨髄性白血病を排除する機構を利用した新規創薬開発の可能性を見出した。それは、これまでの既存の薬剤とは異なる作用起点であることから、既存薬との併用により、より効率的にがんを制御できる可能性がある。