論文 - 詳細
| RRC ID | 85101 |
|---|---|
| 著者 | Noura M, Yasuda T, Kiyoi H, Hayakawa F. |
| タイトル | Induction of T-Cell Differentiation by KLF4 in T-Cell Acute Lymphoblastic Leukemia Cells Harboring Activating Mutation in NOTCH3. |
| ジャーナル | FASEB J |
| Abstract |
Krüppel-like factor 4 (KLF4) exhibits both oncogenic and tumor-suppressive effects depending on the type of cancer and cellular context. In T-cell acute lymphoblastic leukemia (T-ALL), KLF4 expression is silenced by promoter methylation, and the induction of KLF4 suppresses the proliferation of T-ALL cells. Therefore, KLF4 is thought to function as a tumor suppressor in T-ALL cells; however, its role in the differentiation of T-ALL cells remains unclear. Here, we show that KLF4 induced T-cell differentiation and apoptosis in TALL-1 cells harboring an activating mutation in NOTCH3. Mechanistically, KLF4 directly downregulated NOTCH3 expression by binding to its promoter, thereby promoting the differentiation of CD4/CD8 double-positive cells into CD4 single-positive cells, with the differentiated cells subsequently undergoing apoptosis. Furthermore, we found that APTO-253, a small-molecule inducer of KLF4, effectively suppressed cell growth in TALL-1 cells by promoting T-cell differentiation followed by apoptotic cell death. These findings suggest a promising strategy for developing novel differentiation therapies for T-ALL with NOTCH3 mutations. |
| 巻・号 | 39(10) |
| ページ | e70613 |
| 公開日 | 2025-5-31 |
| DOI | 10.1096/fj.202402997R |
| PMID | 40354086 |
| PMC | PMC12068419 |
| MeSH | Apoptosis Cell Differentiation* Cell Line, Tumor Cell Proliferation Humans Kruppel-Like Factor 4 Kruppel-Like Transcription Factors* / genetics Kruppel-Like Transcription Factors* / metabolism Mutation* Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / genetics Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / metabolism Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / pathology Receptor, Notch3* / genetics Receptor, Notch3* / metabolism T-Lymphocytes* / metabolism |
| IF | 4.966 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSIV-TRE-Ubc-KT (RDB12878) pENTR4-H1tetOx1 (RDB07916) CS-RfA-ETBsd (RDB07917) CS-RfA-ETV (RDB08020) |