| Autor: |
Yanxin Chen, Zhengjun Wu, Lingyan Wang, Minhui Lin, Peifang Jiang, Jingjing Wen, Jiazheng Li, Yunda Hong, Xiaoyun Zheng, Xiaozhu Yang, Jing Zheng, Robert Peter Gale, Ting Yang, Jianda Hu |
| Rok vydání: |
2022 |
| Popis: |
Most acute lymphoblastic leukemia (ALL) patients are treated with chemotherapy as primary care. Although treatment response is usually positive, resistance and relapse often occur through unclear mechanisms. Here, we presented clinical and experimental evidence that overexpression of nucleolin (NCL), a multifunctional nucleolar protein, is linked to drug resistance in ALL. By analyzing our patient specimens and an existing database, a strong correlation between the abundance of nucleolin and disease relapse/poor survival was observed. Altering the NCL expression resulted in changes in drug sensitivity in cell lines. High levels of nucleolin could up-regulate components of the ATP-binding cassette transporters via the activation of the ERK pathway, which resulted in a decrease in drug accumulation inside the cells. NCL protein was mainly distributed in the cytoplasm and membrane in ALL cells compared with cell nuclei of normal cells. Moreover, targeting NCL with AS1411, a nucleolin-binding oligonucleotide aptamer, drastically increased sensitivity to chemotherapeutic drugs in cells/patients derived xenograft mice and extended survival of the diseased mice. Our results indicated that NCL could be a prognostic marker and provided initial preclinical evidence that inhibiting nucleolin expression could enhance drug sensitivity during ALL chemotherapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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