Molecular mechanisms of leukemogenesis and stem cell regulation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04227
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Mie University
• Principal Investigator: Nosaka Tetsuya 三重大学, 医学系研究科, 教授 (30218309)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: MLL / Eya2 / E2A-HLF / 白血病 / 染色体転座

Outline of Final Research Achievements

We previously showed that PLZF plays a critical role in MLL-ENL-mediated leukemogenesis, and Eya2, an essential gene for eye development in Drosophila, was found to be important as a downstream molecule of PLZF in the leukemogenesis. Here we report that Eya2 has a critical role in leukemogenesis by E2A-HLF, a responsible gene for one of the most aggressive pediatric lymphoid leukemias, suggesting Eya2 as a possible target for a molecular therapy against therapy-resistant leukemias. Meanwhile, Tet1, one of the upregulated genes downstream of MLL-ENL, has been found to give no effects on the phenotype of MLL-ENL-mediated leukemia, by analyses using Tet1 conditional knockout mice we have developed.

Free Research Field

血液学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

小児の白血病は比較的予後が良いものが多いが、中には予後不良のものがある。小児急性リンパ性白血病の原因遺伝子の一つにE2A-HLFが知られているが、同遺伝子によって発症した白血病は予後が悪く、その分子機構も不明な点が多い。我々はE2A-HLFによって生じる白血病発症の分子機構としてEya2という転写活性化因子の関与を明らかにした。このことによって、難治性白血病に対する将来の分子標的療法の可能性を開いたと言える。