Expression profiling of extramedullary acute myeloid leukemia suggests involvement of epithelial-mesenchymal transition pathways.
Tiziana OttoneG SilvestriniRocco Giovanni PiazzaSerena TravagliniCarmelo GurnariFrancesco MarchesiA M NardozzaE FabianiEnrico AttardiL GuarneraM DivonaP RicciM A Irno ConsalvoS IenziR ArceseA BiagiL FioriM NovelloA MaurielloA VendittiL AnemonaMaria Teresa Teresa VosoPublished in: Leukemia (2023)
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.
Keyphrases
- epithelial mesenchymal transition
- acute myeloid leukemia
- extracellular matrix
- transforming growth factor
- signaling pathway
- allogeneic hematopoietic stem cell transplantation
- cell migration
- transcription factor
- papillary thyroid
- randomized controlled trial
- newly diagnosed
- cell proliferation
- end stage renal disease
- ejection fraction
- genome wide
- single cell
- gene expression
- squamous cell
- rna seq
- poor prognosis
- high throughput
- pseudomonas aeruginosa
- prognostic factors
- lymph node metastasis
- escherichia coli
- dna methylation
- peritoneal dialysis
- childhood cancer
- patient reported outcomes
- binding protein