دورية أكاديمية
CASZ1 upregulates PI3K-AKT-mTOR signaling and promotes T-cell acute lymphoblastic leukemia
| العنوان: | CASZ1 upregulates PI3K-AKT-mTOR signaling and promotes T-cell acute lymphoblastic leukemia |
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| المؤلفون: | Bruno A. Cardoso, Mafalda Duque, Ana Gírio, Rita Fragoso, Mariana L. Oliveira, James R. Allen, Leila R. Martins, Nádia C. Correia, André Bortolini Silveira, Alexandra Veloso, Shunsuke Kimura, Lisa Demoen, Filip Matthijssens, Sima Jeha, Cheng Cheng, Ching-Hon Pui, Ana R. Grosso, João L. Neto, Sérgio F. de Almeida, Pieter Van Vlieberghe, Charles G. Mullighan, J. Andres Yunes, David M. Langenau, Françoise Pflumio, João T. Barata |
| المصدر: | Haematologica, Vol 109, Iss 6 (2023) |
| بيانات النشر: | Ferrata Storti Foundation, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | CASZ1 is a conserved transcription factor involved in neural development, blood vessel assembly and heart morphogenesis. CASZ1 has been implicated in cancer, either suppressing or promoting tumor development depending on the tissue. However, the impact of CASZ1 on hematological tumors remains unknown. Here, we show that the T-cell oncogenic transcription factor TAL1 is a direct positive regulator of CASZ1, that T-cell acute lymphoblastic leukemia (T-ALL) samples at diagnosis overexpress CASZ1b isoform, and that CASZ1b expression in patient samples correlates with PI3K-AKT-mTOR signaling pathway activation. In agreement, overexpression of CASZ1b in both Ba/F3 and T-ALL cells leads to the activation of PI3K signaling pathway, which is required for CASZ1b-mediated transformation of Ba/F3 cells in vitro and malignant expansion in vivo. We further demonstrate that CASZ1b cooperates with activated NOTCH1 to promote T-ALL development in zebrafish, and that CASZ1b protects human T-ALL cells from serum deprivation and treatment with chemotherapeutic drugs. Taken together, our studies indicate that CASZ1b is a TAL1-regulated gene that promotes T-ALL development and resistance to chemotherapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0390-6078 1592-8721 |
| العلاقة: | https://haematologica.org/article/view/11370Test; https://doaj.org/toc/0390-6078Test; https://doaj.org/toc/1592-8721Test |
| DOI: | 10.3324/haematol.2023.282854 |
| الوصول الحر: | https://doaj.org/article/e0e1c7294ff1479dbb2741b0c1056932Test |
| رقم الانضمام: | edsdoj.0e1c7294ff1479dbb2741b0c1056932 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 03906078 15928721 |
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| DOI: | 10.3324/haematol.2023.282854 |