Deciphering leukemia development and maintenance from the perspective of functions of fusion genes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02645
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Tsuzuki Shinobu 愛知医科大学, 医学部, 教授 (00342965)
• Co-Investigator(Kenkyū-buntansha): 安田 貴彦 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, 分子診断研究室長 (20723977)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 急性リンパ性白血病 / MEF2D / CRLF2

Outline of Final Research Achievements

Acute lymphocytic leukemia harboring abnormalities in MEF2D or CRLF2 genes is associated with poor clinical outcomes. (1) In the type with an abnormality (fusion gene) in the MEF2D gene, we found that (a) this abnormal gene induces pre-B cell receptor on the cell surface, which plays essential roles for the growth and maintenance of leukemia. (b) Therefore, drugs weakening its expression have therapeutic efficacy. (2) In the type with an abnormality in the CRLF2 gene, this gene activates an enzyme called JAK, but the therapeutic effect of inhibitors of JAK itself is low. Here, we clarified a part of the reason and identified drugs exploitable as a countermeasure.

Free Research Field

造血器腫瘍学

Academic Significance and Societal Importance of the Research Achievements

急性リンパ性白血病の成人における長期生存率は30%と不良で、治療成績の比較的良い小児においても抗がん剤・放射線治療の長期的悪影響は無視できない。白血病の原因遺伝子の機能解析を通じた治療戦略ならびに新規治療法の開発が必要である。本研究では、２つの予後不良タイプを対象に、白血病がどのような機構で維持され、また、治療不応性を示すのか、その一端を明らかにし、その対策薬を同定した。この対策薬は動物での治療実験でも効果を確認でき、ヒトへの応用が示唆される。