A5036115192- Chronic Lymphocytic Leukemia Research
- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- Immunodeficiency and Autoimmune Disorders
- Acute Lymphoblastic Leukemia research
- Genetics and Neurodevelopmental Disorders
- PI3K/AKT/mTOR signaling in cancer
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- Lymphoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Advanced Breast Cancer Therapies
- SARS-CoV-2 and COVID-19 Research
- Ion Transport and Channel Regulation
- Calcium signaling and nucleotide metabolism
- CAR-T cell therapy research
- Evolutionary Algorithms and Applications
- Cancer-related gene regulation
- Cell death mechanisms and regulation
- DNA Repair Mechanisms
- Erythropoietin and Anemia Treatment
- Congenital heart defects research
University of Perugia
2018-2025
Istituto Oncologico Veneto
2024
Misericordia University
2023
Institute of Hydrology of the Slovak Academy of Sciences
2019
Dysregulated NOTCH1 signaling, by either gene mutations or microenvironment interactions, has been increasingly linked to chronic lymphocytic leukemia (CLL). Thus, inhibiting activity represents a potential therapeutic opportunity for this disease. Using expression-based screening, we identified the calcium channel modulator bepridil as new pathway inhibitor. In primary CLL cells, induced selective apoptosis even in presence of protective stroma. Cytotoxic effects were independent mutation...
Ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), has improved the outcomes of chronic lymphocytic leukemia (CLL), but primary resistance or relapse are issues increasing significance. While predominant mechanism action BTKi is B-cell receptor (BCR) blockade, many off-target effects unknown. We investigated potential interactions between BCR pathway and NOTCH1 activity in ibrutinib-treated CLL to identify new mechanisms therapy markers monitor disease response.NOTCH activations was...
Abstract Richter’s transformation (RT) is an aggressive lymphoma occurring upon progression from chronic lymphocytic leukemia (CLL). Despite advances in deciphering the RT genetic architecture, mechanisms driving this disease remain unknown. BCOR disruptive mutations were found CLL and frequently associated with NOTCH1 aberrations, a common feature RT. We engineered mice to knock-out Bcor B cells of Eμ- TCL1 mice. loss resulted alterations cell compartment favored into reduced survival...
Chronic lymphocytic leukemia (CLL) is an incurable disorder associated with alterations in several pathways essential for survival and proliferation. Despite the advances made CLL therapy new target agents, some cases, relapses resistance could occur, making discovery of alternatives to manage refractoriness necessary. To provide therapeutic strategies CLL, we investigated anti-leukemic activity silver nanoparticles (AgNPs), whose impact on cells has been poorly explored.We studied action...
Constitutive activation of NOTCH1-wild-type (NT1-WT) signaling is associated with poor outcomes in chronic lymphocytic leukemia (CLL), and NOTCH1 mutation (c.7541_7542delCT), which potentiates signaling, worsens the prognosis. However, specific mechanisms deregulation are still poorly understood. Accumulative evidence mentioned endoplasmic reticulum (ER) stress/unfolded protein response (UPR) as a key targetable pathway CLL. In this study, we investigated impact on CLL cell to ER stress...
To investigate Chronic Lymphocytic Leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1-mutated CLL, detected subclonal mutations 57% CD34+/CD38- HSCs. mutation was present 66% CD34+/CD38+ progenitor displaying an increased mutational burden compared to Flow cytometric analysis revealed significantly higher activation and from CLL patients, regardless healthy donors. Activated signaling resulted overexpression of the target...
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,...
NOTCH1 mutations and deregulated signal have been commonly found in chronic lymphocytic leukemia (CLL) patients. Whereas the impact of on clinical course CLL has widely studied, prognostic role activation remains to be defined. Here, we analyzed NOTCH1/NOTCH2 (ICN1/ICN2) expression JAGGED1 (JAG1) 163 patients evaluated their TTFT (Time To First Treatment) OS (Overall Survival). (ICN1+) was 120/163 (73.6%) Among them, 63 (52.5%) were mutated (ICN1+/mutated) 57 (47.5%) wild type (ICN1+/WT)....
Increased expression of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) often correlates with tumor aggressiveness and drug resistance in cancer. We have recently reported that BCAT1 was overexpressed a subgroup T-cell acute lymphoblastic (T-ALL) samples, especially those NOTCH1 activating mutations. Interestingly, BCAT1-depleted cells showed pronounced sensitivity to DNA-damaging agents such as etoposide; however, how regulates this remains uncertain. Here, we provide further clues...
NOTCH1 alterations have been associated with chronic lymphocytic leukemia (CLL), but the molecular mechanisms underlying activation in CLL cells are not completely understood. Here, we show that GSK3β downregulates constitutive levels of active intracellular domain (N1-ICD) cells. Indeed, silencing by small interfering RNA increases N1-ICD levels, whereas expression an mutant reduces them. Additionally, inhibitor SB216763 enhances stability at a concentration which it also cell viability. We...
Summary In chronic lymphocytic leukaemia (CLL) the efficacy of SARS‐CoV‐2 vaccination remains unclear as most studies have focused on humoral responses. Here we comprehensively examined and cellular responses to vaccine in CLL patients. Seroconversion was observed 55.2% with lower rate antibody titres treated T‐cell were detected a significant fraction CD4 + CD8 frequencies significantly increased independent serology higher levels cells patients under Bruton tyrosine kinase (BTK) or B‐cell...
A 57-year-old man affected by high-risk progressive chronic lymphocytic leukemia (CLL), primary resistant to first-line chemoimmunotherapy, developed a type lymphomatoid papulosis (LyP) during second progression of CLL. The two blood tumor entities were clonally unrelated. LyP presented with diffuse (>90% body surface area) cutaneous rash and was characterized intensely pruriginous dusky nodules (n = 10) red flat-topped papules 60). No response topical corticosteroids psoralen plus...
<p>Figure S10</p>
<p>Figure S4</p>
<p>Figure S3</p>
<p>Figure S5</p>
<p>Figure S7</p>