Expression profiling of extramedullary acute myeloid leukemia suggests involvement of epithelial-mesenchymal transition pathways.

Autor: Ottone T; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.; Santa Lucia Foundation, I.R.C.C.S., Neuro-Oncohematology, Rome, Italy., Silvestrini G; Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy., Piazza R; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy., Travaglini S; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy., Gurnari C; Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy.; Translational Hematology and Oncology Research Department, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, 44106, USA., Marchesi F; Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Nardozza AM; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy., Fabiani E; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.; Saint Camillus International University of Health Sciences, Rome, Italy., Attardi E; Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy., Guarnera L; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy., Divona M; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.; Saint Camillus International University of Health Sciences, Rome, Italy., Ricci P; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy., Irno Consalvo MA; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy., Ienzi S; Department of Anatomical Pathology, F. Spaziani Hospital, Frosinone, Italy., Arcese R; Department of Anatomical Pathology, F. Spaziani Hospital, Frosinone, Italy., Biagi A; Hematology and Transplant Unit, Santa Maria Goretti Hospital, AUSL, Latina, Italy., Fiori L; Hematology and Transplant Unit, Santa Maria Goretti Hospital, AUSL, Latina, Italy., Novello M; Pathology Department, IRCCS-Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy., Mauriello A; Department of Experimental Medicine, Faculty of Medicine, Tor Vergata University, Rome, Italy., Venditti A; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy., Anemona L; Department of Experimental Medicine, Faculty of Medicine, Tor Vergata University, Rome, Italy., Voso MT; Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy. voso@med.uniroma2.it.; Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy. voso@med.uniroma2.it.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2023 Dec; Vol. 37 (12), pp. 2383-2394. Date of Electronic Publication: 2023 Oct 06.
DOI: 10.1038/s41375-023-02054-0
Abstrakt: Extramedullary (EM) colonization is a rare complication of acute myeloid leukemia (AML), occurring in about 10% of patients, but the processes underlying tissue invasion are not entirely characterized. Through the application of RNAseq technology, we examined the transcriptome profile of 13 AMLs, 9 of whom presented an EM localization. Our analysis revealed significant deregulation within the extracellular matrix (ECM)-receptor interaction and focal-adhesion pathways, specifically in the EM sites. The transcription factor TWIST1, which is known to impact on cancer invasion by dysregulating epithelial-mesenchymal-transition (EMT) processes, was significantly upregulated in EM-AML. To test the functional impact of TWIST1 overexpression, we treated OCI-AML3s with TWIST1-siRNA or metformin, a drug known to inhibit tumor progression in cancer models. After 48 h, we showed downregulation of TWIST1, and of the EMT-related genes FN1 and SNAI2. This was associated with significant impairment of migration and invasion processes by Boyden chamber assays. Our study shed light on the molecular mechanisms associated with EM tissue invasion in AML, and on the ability of metformin to interfere with key players of this process. TWIST1 may configure as candidate marker of EM-AML progression, and inhibition of EMT-pathways may represent an innovative therapeutic intervention to prevent or treat this complication.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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