A5075052618- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Vitamin C and Antioxidants Research
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- Ubiquitin and proteasome pathways
- Advanced biosensing and bioanalysis techniques
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Kruppel-like factors research
- Protein Degradation and Inhibitors
- Sarcoma Diagnosis and Treatment
- Genomics, phytochemicals, and oxidative stress
- interferon and immune responses
- Animal Genetics and Reproduction
- Molecular Biology Techniques and Applications
- Drug Transport and Resistance Mechanisms
- Antioxidant Activity and Oxidative Stress
- Multiple Myeloma Research and Treatments
- Gene expression and cancer classification
- Reproductive System and Pregnancy
University of Rome Tor Vergata
2018-2024
Fondazione Santa Lucia
2022-2023
The increasing knowledge of molecular genetics acute myeloid leukemia (AML) necessitated the update previous diagnostic and prognostic schemes, which resulted in development World Health Organization (WHO), International Consensus Classification (ICC), new European LeukemiaNet (ELN) recommendations 2022. We aimed to provide a real-world application models, unravel differences similarities, test their implementation clinical AML diagnosis. A total 1001 patients diagnosed with were...
Abstract Despite the high probability of cure patients with acute promyelocytic leukemia (APL), mechanisms relapse are still largely unclear. Mutational profiling at diagnosis and/or may help to identify APL needing frequent molecular monitoring and early treatment intervention. Using an NGS approach including a 31 myeloid gene‐panel, we tested BM samples 44 APLs time diagnosis, relapse. Mutations in PML RARA genes were studied using customized‐NGS‐RNA panel. Patients relapsing after...
Therapy-related myeloid neoplasms (t-MN) arise after a documented history of chemo/radiotherapy as treatment for an unrelated condition and account 10–20% myelodysplastic syndromes acute leukemia. T-MN are characterized by specific genetic signature, aggressive features dismal prognosis. The nomenclature the subsets these conditions have changed frequently over time, despite fact that, in last classification, they lost their autonomous entity status became disease qualifiers, recognition...
Key Points RA synergizes with the N-glycosylation inhibitor tunicamycin and ATO to induce AML cell death via generation of ER oxidative stress.
In the present study, we characterized metabolic background of different Acute Myeloid Leukemias’ (AMLs) cells and described a heterogeneous highly flexible energetic metabolism. Using Seahorse XF Agilent, compared metabolism normal hematopoietic progenitors with that primary AML blasts five cell lines. We assessed efficacy mechanism action association high doses ascorbate, powerful oxidant, inhibitor buformin, which inhibits mitochondrial complex I completely shuts down contributions in ATP...
Once the diagnostic suspicion of acute promyelocytic leukemia (APL) has been raised, international guidelines recommend prompt initiation tailored therapy and supportive care, while awaiting for genetic confirmation diagnosis, identification specific PML/RARA isoform by reverse transcriptase polymerase chain reaction (RT-PCR). Depending on PML break point, usually located within intron 6, exon or 3, different transcript isoforms may be generated, that is, long (bcr1), variant (bcr2), short...
Vitamin C has been shown to play a significant role in suppressing progression of leukemia through epigenetic mechanisms. We aimed study the vitamin acute myeloid (AML) biology and clinical course. To this purpose, plasma levels at diagnosis 62 patients with AML (including 5 cases promyelocytic leukemia, APL),7 myelodysplastic syndrome (MDS), 15 healthy donors (HDs) were studied. As controls, vitamins A E analysed. Expression main transporters TET2 enzyme investigated by specific RQ-PCR...
Abstract Bone marrow mesenchymal stem cells (BM-MSCs) exhibit multiple abnormalities in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), including reduced proliferative clonogenic capacity, altered morphology, impaired immunoregulatory properties capacity to support hematopoiesis. Here, we investigated expression of the FOXM1 gene, a transcription factor driving G2/M gene expression, BM-MSCs isolated from patients with MDS AML, de novo therapy-related, compared healthy...
Acute myeloid leukemia (AML) with FLT3-ITD mutations (FLT3-ITDmut) remains a therapeutic challenge, still high relapse rate, despite targeted treatment tyrosine kinase inhibitors. In this disease, the CD34/CD123/CD25/CD99+ leukemic precursor cells (LPCs) phenotype predicts for FLT3-ITD-positivity. The aim of study was to characterize distribution mutation in different progenitor cell subsets shed light on subclonal architecture FLT3-ITDmut AML. Using high-speed sorting, we sequentially...
Summary Essential for cell survival, the 90 kD Heat Shock Proteins ( HSP 90) are molecular chaperons required conformational stabilization and trafficking of numerous client proteins. Functional is stability AKT , a serine‐threonine kinase phosphorylated in response to growth factor stimulation. plays crucial regulatory role differentiation, cycle, transcription, translation, metabolism apoptosis. Acute promyelocytic leukaemia APL ) characterized by presence leukaemia/retinoic acid receptor...
To follow mast cells (MCs) distribution during aging and inflammation, we characterized two transgenic mouse models in which the EGFP expression is controlled by 9 kb or 12 of Kit gene promoter, defined as p18 p70, respectively. We detected EGFP-positive serosal surfaces peritoneum, pleuras pericardium, mucosal cavities, connective tissue almost all organs including gonads but not mice. By FACS immunofluorescence for FcεR1, β7-integrin, found that these positive were MCs. In non-inflammatory...
Acute myeloid leukemia (AML) patients bearing the ITD mutation in tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and high risk of relapse. FLT3-ITD is retained endoplasmic reticulum (ER) generates intrinsic proteotoxic stress. We devised strategy based on stress, generated by combination low doses differentiating agent retinoic acid (R), proteasome inhibitor bortezomib (B), oxidative stress inducer arsenic trioxide (A). treated FLT3-ITD+ AML cells with aforementioned...
NRF2 (NF-E2 p45-related factor 2) orchestrates cellular adaptive responses to stress. Its quantity and subcellular location is controlled through a complex network its activity increases during redox perturbation, inflammation, growth stimulation, energy fluxes. Even before all-trans retinoic acid (ATRA) treatment era it was common experience that acute promyelocytic leukemia (APL) cells are highly sensitive first line chemotherapy. Since we demonstrated how high doses of ascorbate (ASC)...
Acute myeloid leukemia (AML) with inv(16) is typically associated a favourable prognosis. However, up to 40 % of patients will eventually experience disease relapse. Herein, we dissected the genomic and transcriptomic profile AML identify potential prognostic markers therapeutic vulnerabilities. Sequencing data from 222 diagnostic samples, including 44 relapse/refractory patients, revealed median 1 concomitant additional mutation, cooperating in leukemogenesis. Notably, mutational landscape...