The mechanism of leukemic transformation from myeloproliferative neoplasms

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08399
• 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: Fukushima Medical University
• Principal Investigator: Ueda Koki 福島県立医科大学, 医学部, 講師 (80632190)
• Co-Investigator(Kenkyū-buntansha): 池田 和彦 福島県立医科大学, 医学部, 教授 (90381392) ; 三村 耕作 福島県立医科大学, 医学部, 准教授 (90568031)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨髄増殖性腫瘍 / 急性転化 / 急性骨髄性白血病

Outline of Final Research Achievements

To elucidate critical factors to induce leukemic transformation from myeloproliferative neoplasms (MPN), we generated a murine model which slowly develop acute myeloid leukemia (AML) from moderate phenotypes of MPN. We crossbred Calr-10d mice with Ezh2-KO mice, and obtained Calr-10d, Ezh2-KO, Calr-10d;Ezh2-KO respectively. We observed these mice, and found that only Calr-10d;Ezh2-KO mice died with AML or severe MPN during age 10 to 18 months. Calr-10d and Ezh2-KO mice lived nearly 24 months.Upregulation of polycomb target genes were observed in hematopoietic stem cells (HSCs) of Calr-10d;Ezh2-KO mice.Presently, we are analyzing HSCs of moribund AML and MPN mice, and we are expecting to detect important factors for leukemic transformation.

Free Research Field

骨髄系腫瘍

Academic Significance and Societal Importance of the Research Achievements

骨髄増殖性腫瘍の治療は進歩していますが、白血病への進行を阻止する方法は確立していません。造血細胞にどのような変化が起きると白血病に進行するのかを明らかにするためには、患者さんの骨髄を頻回に採取して、白血病に進行した患者さんと進行しなかった患者さんの違いを調べるのが一番ですが、それでは患者さんの負担が大きすぎます。今回の研究成果から、マウスを用いて病態解明を進めることが期待できます。