Significance of evaluating RUNX3 expression in acute myeloid leukemia

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08976
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: National Cancer Center Japan
• Principal Investigator: Matsushita Hiromichi 国立研究開発法人国立がん研究センター, 中央病院, 医長 (50286481)
• Co-Investigator(Kenkyū-buntansha): 安藤 潔 東海大学, 医学部, 教授 (70176014)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: RUNX3 / 急性骨髄性白血病 / 遺伝子変異 / 予後不良因子

Outline of Final Research Achievements

We previously elucidated that FLT3-ITD, a poor prognostic factor in acute myeloid leukemia (AML), induces Ara-C resistance through the upregulation of RUNX3. The current study aimed to investigate whether the RUNX3 expression is an excellent biomarker that predicts the prognosis of AML. In 71 AML cases with various genetic mutations, the cases with lower RUNX3 expression tended to have better overall survival (OS) than higher expression without statistical significances. Forty AML cases with normal karyotype also showed no difference in OS, when the cases with higher and lower RUNX3 expression were compared. Additionally, the mutations in epigenetic associated-genes such as TET2, DNMT3A, IDH2 and ASXL1 as well as the FLT3-ITD mutation did not affect the RUNX3 expression. Although there have been no apparent evidences that showed the RUNX3 expression is a useful biomarker for AML thus far, we will continue to examine in detail the significance of RUNX3 expression in AML.

Free Research Field

臨床検査学

Academic Significance and Societal Importance of the Research Achievements

急性骨髄性白血病（AML）の悪性度は症例によって様々であり、染色体・遺伝子異常などの指標（＝バイオマーカー）を参考にしながら治療方法を決定することが多い。今回の研究では、私達が抗がん剤耐性に関係すると報告してきたRUNX3遺伝子についてバイオマーカーとしての可能性を検討した。検討したAML71症例全体ではRUNX3遺伝子の量の低い方が生存率が高い傾向であったが、まだ十分な結果は得られていない。今後さらなる解析を続けて、RUNX3遺伝子の量を検索することの有用性を明らかにしていきたい。