Notch signaling as a therapeutic target in refractory acute myeloid leukemia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09915
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: Kato Takayasu 筑波大学, 医学医療系, 講師 (20646591)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 急性骨髄性白血病 / NOTCHシグナル / 骨髄微小環境

Outline of Final Research Achievements

This study targeted acute myeloid leukemia (AML) and aimed to identify new therapeutic targets and overcome leukemia by clarifying the interaction between AML cells and bone marrow microenvironment (bone marrow stromal cells). As a result of the research, when NOTCH signal was knocked out in the whole bone marrow microenvironment, the proliferation of AML cells was enhanced. Leukemic mice, which are recipient mice lacking the NOTCH signal in the whole bone marrow microenvironment, died very early after transplantation and were difficult to analyze. Therefore, we created conditional knock out mice that lack the NOTCH signal only in specific bone marrow stromal cells. We discovered that this mouse causes a differentiation disorder in the erythroid lineage, and AML mouse model using this mouse is currently being analyzed.

Free Research Field

造血器腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究はマウス白血病モデルとヒト検体を用いた解析であり、造血細胞と造血支持細胞（骨髄ストローマ細胞）の双方の異常が白血病発症機構に関わるとういう点が、学術的意義である。
またAMLの現行治療による生存率は約40%であり、さらなる病態解明が必要である。特に本疾患が実際に好発する60歳代以降では、治療法の進歩に乏しい。本研究を発展させる事で、より副作用が少なく有効な治療法の開発に対する社会的意義が期待される。