CASZ1 upregulates PI3K-AKT-mTOR signaling and promotes T-cell acute lymphoblastic leukemia.

Autor:	Cardoso BA; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon., Duque M; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon., Gírio A; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon., Fragoso R; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon., Oliveira ML; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon., Allen JR; MGH Pathology and Harvard Medical School, Charlestown MA 02129., Martins LR; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon., Correia NC; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon., Silveira AB; Laboratório de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP., Veloso A; MGH Pathology and Harvard Medical School, Charlestown MA 02129., Kimura S; Department of Pathology, Center of Excellence for Leukemia Studies, and Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis TN., Demoen L; Department of Biomolecular Medicine, Ghent University, and Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Matthijssens F; Department of Biomolecular Medicine, Ghent University, and Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Jeha S; Department of Oncology, St. Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis TN, US; Department of Global Pediatric Medicine, St. Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis TN., Cheng C; Department of Biostatistics, St. Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis TN., Pui CH; Department of Oncology, St. Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis TN, US; Department of Global Pediatric Medicine, St. Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis TN, US; Department of Pathology, St. Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis TN., Grosso AR; Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica., Neto JL; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon., De Almeida SF; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon., Van Vlieberghe P; Department of Biomolecular Medicine, Ghent University, and Cancer Research Institute Ghent (CRIG), Ghent, Belgium., Mullighan CG; Department of Pathology, Center of Excellence for Leukemia Studies, and Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis TN., Yunes JA; Laboratório de Biologia Molecular, Centro Infantil Boldrini, Campinas, SP., Langenau DM; MGH Pathology and Harvard Medical School, Charlestown MA 02129., Pflumio F; Université Paris-Saclay, INSERM, iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, F-92265, Fontenay-aux-Roses, France; OPALE Carnot Institute, The Organization for Partnerships in Leukemia, Saint-Louis Hospital, 75010 Paris., Barata JT; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon. joao_barata@medicina.ulisboa.pt.
Jazyk:	angličtina
Zdroj:	Haematologica [Haematologica] 2024 Jun 01; Vol. 109 (6), pp. 1713-1725. Date of Electronic Publication: 2024 Jun 01.
DOI:	10.3324/haematol.2023.282854
Abstrakt:	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.
Databáze:	MEDLINE
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