Elucidate the importance of MPL in the pathogenesis of hematological diseases caused by abnormal EVI1 expression

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16105
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Tohoku University
• Principal Investigator: Katayama Saori 東北大学, 東北メディカル・メガバンク機構, 助教 (50812278)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: EVI1 / GATA2 / 巨核球 / 血小板 / 白血病

Outline of Final Research Achievements

Leukemia caused by chromosome 3 inversions/translocations is characterized by thrombocytosis. In this leukemia, overexpression of the EVI1 gene and decreased expression of GATA2 occur. In this study, we investigated the mechanism of thrombocytosis using a mouse model and found that overexpression of EVI1 caused an increase in megakaryocytes and their progenitors even before the onset of leukemia. In addition, the simultaneous reproduction of EVI1 gene overexpression and GATA2 gene downregulation reproduced leukemia with thrombocytosis. This study revealed that the EVI1 and GATA2 genes cooperatively leads to the development of leukemia with thrombocytosis.

Free Research Field

血液および腫瘍内科学

Academic Significance and Societal Importance of the Research Achievements

3番染色体長腕q21とq26との逆位・転座は、急性骨髄性白血病の約1-2％でみられ、予後不良因子として知られている。本研究ではこの予後不良白血病の特徴である巨核球・血小板増多を再現する系を確立した。巨核球は造血幹細胞の静止期維持や増殖の制御に関与していることが報告されており、巨核球が白血病幹細胞を静止期にとどめることが白血病の予後不良に関与している可能性が考えられる。本研究で確立した3q21q26-EVI1::Gata2+/gfpマウスモデルを活用してEVI1による巨核球分化の制御機構を知ることが予後不良の白血病の治療につながる知見をもたらすことが期待される。