王麗婷Wang, Li-Ting葉立恆Ye, Li-Heng2025-12-092028-11-302024https://etds.lib.ntnu.edu.tw/thesis/detail/6cd5c5cd57692ec49233ee46f2d487fa/http://rportal.lib.ntnu.edu.tw/handle/20.500.12235/125657急性淋巴性白血病是兒童最常見的癌症之一，儘管目前治療方法越來越多，但有部分患者的預後仍不佳且易復發，復發原因被推測與癌症幹細胞相關。先前研究已經明瞭 RUNX1 對於造血幹細胞、急性淋巴性白血病及該疾病預後中都扮演重要角色，RUNX1 為轉錄因子，然而對於其作用及機制在急性淋巴性白血病中仍不清楚。急性淋巴性白血病具有不同亞型，多半以何種譜系的增生導致而命名，如 T 細胞或 B 細胞急性淋巴性白血病，本篇則專注在 B 細胞前驅細胞急性淋巴性白血病 （BCP-ALL）。在研究中首先確認患者的預後與 RUNX1 表現量的關係，此外也發現過度表達RUNX1的急性淋巴性白血病細胞會導致細胞增生增加、分泌 Galectin-9 到胞外能力提升及發現在基因層面及蛋白質中 ISX 及幹性相關的表現量也顯著提升，因此透過 Ch-IP 及冷光報導分析發現 RUNX1 藉由結合在 ISX 的啟動子中-40~0序列上。透過靜默 RUNX1 發現 RUNX1 對於ISX、LGALS9、幹性、增生基因表現是必要的。並且利用 RUNX1 以及 ISX shRNA 的細胞轉染驗證 RUNX1 透過 ISX 調控細胞增生能力、惡性程度及 LGALS9 與幹性基因的表達。最終在病人檢體中發現 RUNX1 與 ISX 兩者間具有正相關性，並且觀察到與 RUNX1 高表現預後不佳的情況相同：ISX 高表現病人也預後不佳。Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer. Despite advancements in therapy, some patients face a poor prognosis and risks of relapse linked to cancer stem cells. Research highlights RUNX1's pivotal role in hematopoietic stem cells, ALL, and disease prognosis, yet its exact mechanisms remain unclear. ALL encompasses subtypes like T-cell or B-cell ALL, with this study focusing on B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This study initially elucidated the correlation between patient prognosis and RUNX1 expression. Overexpression of RUNX1 increased cell proliferation and elevated ISX, LGALS9, and stemness genes at both transcriptional and protein levels. Ch-IP and luciferase reporter assay pinpointed RUNX1 binding to the -40 to 0 sequence within the ISX promoter. RUNX1 silencing experiments underscored RUNX1's necessity for ISX, LGALS9, stemness, and proliferation gene expression. Transfection with RUNX1 and ISX shRNA substantiated RUNX1's regulatory role via ISX on the aforementioned gene expressions. Finally, a strong positive correlation between RUNX1 and ISX was validated in patient samples, with high ISX expression correlating with a poor prognosis, paralleling findings with high RUNX1 expression.B細胞急性淋巴性白血病癌症幹細胞RUNX1ISXGalectin-9BCP-ALLcancer stem cellRUNX1ISXGalectin-9學術論文