Elucidation of hematopoietic regulatory mechanisms via lipid balance

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08724
• 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: Kato Takayasu 筑波大学, 医学医療系, 講師 (20646591)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Elovl6 / 白血病 / 造血幹細胞 / PI3K / CXCL12 / 急性骨髄性白血病 / 遊走

Outline of Final Research Achievements

This study examined whether altering intracellular fatty acid composition could be a novel treatment for acute myeloid leukemia (AML). Since ELOVL6, an enzyme that elongates the carbon number of fatty acids, affects fatty acid composition, this study used Elovl6-deficient (E6KO) mice to examine its effects on hematopoietic stem cells and AML. When E6KO bone marrow cells were transplanted into normal mice, no hematopoiesis was observed in the bone marrow. Furthermore, when leukemia genes were introduced into E6KO bone marrow cells and transplanted into wild-type mice, they did not develop AML. These findings indicate that the signals controlling cell motility are reduced by changes in fatty acid composition. These results indicate that altering fatty acid composition may lead to the treatment of AML.

Free Research Field

造血器腫瘍

Academic Significance and Societal Importance of the Research Achievements

急性骨髄性白血病（AML）の治癒率は向上しましたが、その恩恵を受けてきたのは主に若・壮年者です。しかしAMLを発症しやすい60歳代以降にも適用できる副作用の少ない新規治療法の開発が必須です。本研究ではElovl6による‘脂質の質’の変化が、造血幹細胞の生着とAMLの発症を制御していることを発見しました。すなわち、ELOVL6制御によって脂肪酸バランスを変化させることで、AML新規治療法につながる可能性を世界で初めて示しました。Elovl6を阻害する治療法では、副作用で造血抑制を生じる可能性は小さいと予想されます。今後‘脂肪酸の質’を標的とした新規白血病治療法開発への進展が期待されます。