- Chronic Lymphocytic Leukemia Research
- Acute Myeloid Leukemia Research
- Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- CAR-T cell therapy research
- Vascular Malformations Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Vascular Malformations and Hemangiomas
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Protein Degradation and Inhibitors
University of Parma
2022-2024
University of Ferrara
2022-2024
University of Amsterdam
2024
Amsterdam University Medical Centers
2024
NOTCH1 PEST domain mutations are often seen in hematopoietic malignancies, including T-cell acute lymphoblastic leukemia (T-ALL), chronic lymphocytic (CLL), splenic marginal zone lymphoma (SMZL), mantle cell (MCL), and diffuse large B-cell (DLBCL). These play a key role the development progression of lymphoproliferative tumors by increasing Notch signaling and, consequently, promoting proliferation, survival, migration, suppressing apoptosis. There is currently no specific treatment...
Autologous T-cell-based therapies, such as chimeric antigen receptor (CAR) T-cell therapy, exhibit low success rates in chronic lymphocytic leukemia (CLL) and correlate with a dysfunctional phenotype observed patients. Despite various proposed mechanisms of dysfunction CLL, the specific CLL-derived factors responsible remain unidentified. This study aimed to investigate through which CLL cells suppress CAR activation function. We found that T get activated, albeit delayed fashion,...
Genomic studies have identified recurrent somatic alterations in genes involved DNA methylation and post-translational histone modifications acute lymphoblastic leukemia (ALL), suggesting new opportunities for therapeutic interventions. In this study, we G9a/EHMT2 as a potential target T-ALL through the intersection of epigenome-centered shRNA chemical screens. We subsequently validated G9a with low-throughput CRISPR-Cas9-based targeting catalytic SET-domain testing inhibitors vitro, 3D,...
The mechanisms underlying the success of propranolol in treatment infantile hemangioma (IH) remain elusive and do not fully explain rapid regression hemangiomatous lesions following drug administration. As autophagy is critically implicated vascular homeostasis, we determined whether β-blockers trigger autophagic flux on hemangioma-derived endothelial cells (Hem-ECs) vitro. Fresh tissue specimens, surgically removed for therapeutic purpose to seven children affected by proliferative IH, were...
Abstract The overexpression of the ecotropic viral integration site-1 gene ( EVI1/MECOM ) marks most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage intersectionality high-throughput cell-based and expression screens selective pan-histone deacetylase inhibitors (HDACis) emerge as potent repressors EVI1 . To understand mechanism driving on-target anti-leukemia activity this compound class, here we dissect dynamics bone marrow cells...
Background: Gain-of-function NOTCH1 mutations are the most common genetic abnormality in T-cell Acute Lymphoblastic Leukemia (T-ALL), accounting for 55-60% of cases. Consequently, modulators Notch pathway, such as γ-secretase inhibitors (GSI), would be expected to have clinical efficacy (Rao, Cancer Res 2009). However, their application was limited by an excess toxicity due suppression wild-type (WT) proteins normal tissue (Deangelo, JCO 2006; Doody, Alzherimer’s Ther 2015). In past, we...