Analyses of hematopoietic niche in hematologic malignancy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08316
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Nishikii Hidekazu 筑波大学, 医学医療系, 准教授 (30512834)
• Co-Investigator(Kenkyū-buntansha): 加藤 貴康 筑波大学, 医学医療系, 講師 (20646591) ; 日下部 学 筑波大学, 医学医療系, 講師 (40804381) ; 小原 直 筑波大学, 医学医療系, 教授 (70422178) ; 横山 泰久 筑波大学, 医学医療系, 講師 (70512820)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 造血幹細胞ニッチ / 造血幹細胞 / 急性骨髄性白血病

Outline of Final Research Achievements

To clarify how bone marrow environments are affected in hematopoietic malignancies, we established leukemic mice by introducing MLL-AF9 gene, and analyzed the detailed process which the normal hematopoietic system disrupts in the leukemic bone marrow environment. Residual hematopoietic stem cells, mesenchymal stem cells, perivascular stromal cells, and vascular endothelial cells were isolated from these mice and gene expression analysis was performed. The results showed that hematopoietic stem cell function was abrogated during the the proliferation of leukemic cells. Further, leukemic cells secrete multiple inflammatory and aging-inducing cytokines, resulting in the dysfunction of hematopoietic niche cells, which might be the cause of normal hematopoietic disorders in the leukemic environment. We are currently seeking the therapeutic targets for hematopoietic defect in leukemic environments.

Free Research Field

造血システム・造血幹細胞

Academic Significance and Societal Importance of the Research Achievements

白血病における臓器障害の本態である正常造血システムの破綻は、腫瘍細胞の増殖による正常造血の場の機械的な現象が主な原因と考えられてきたが、本研究結果はむしろ正常造血システムの機能異常が直接的な造血異常に関わっていることを直接的に示している。この研究結果から単純な殺細胞性の抗がん剤治療から正常造血システムの機能維持を目的とした新規治療戦略の構築を目指している。