4 results on '"Baldazzi, Carmen"'
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2. Chromothripsis in acute myeloid leukemia: biological features and impact on survival
- Author
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Fontana, Maria Chiara, Marconi, Giovanni, Feenstra, Jelena D. Milosevic, Fonzi, Eugenio, Papayannidis, Cristina, Ghelli Luserna di Rorá, Andrea, Padella, Antonella, Solli, Vincenza, Franchini, Eugenia, Ottaviani, Emanuela, Ferrari, Anna, Baldazzi, Carmen, Testoni, Nicoletta, Iacobucci, Ilaria, Soverini, Simona, Haferlach, Torsten, Guadagnuolo, Viviana, Semerad, Lukas, Doubek, Michael, Steurer, Michael, Racil, Zdenek, Paolini, Stefania, Manfrini, Marco, Cavo, Michele, Simonetti, Giorgia, Kralovics, Robert, and Martinelli, Giovanni
- Published
- 2018
- Full Text
- View/download PDF
3. Integrated genomic-metabolic classification of acute myeloid leukemia defines a subgroup with NPM1and cohesin/DNA damage mutations
- Author
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Simonetti, Giorgia, Mengucci, Carlo, Padella, Antonella, Fonzi, Eugenio, Picone, Gianfranco, Delpino, Claudio, Nanni, Jacopo, De Tommaso, Rossella, Franchini, Eugenia, Papayannidis, Cristina, Marconi, Giovanni, Pazzaglia, Martina, Perricone, Margherita, Scarpi, Emanuela, Fontana, Maria Chiara, Bruno, Samantha, Tebaldi, Michela, Ferrari, Anna, Bochicchio, Maria Teresa, Ghelli Luserna Di Rorà, Andrea, Ghetti, Martina, Napolitano, Roberta, Astolfi, Annalisa, Baldazzi, Carmen, Guadagnuolo, Viviana, Ottaviani, Emanuela, Iacobucci, Ilaria, Cavo, Michele, Castellani, Gastone, Haferlach, Torsten, Remondini, Daniel, Capozzi, Francesco, and Martinelli, Giovanni
- Abstract
Although targeting of cell metabolism is a promising therapeutic strategy in acute myeloid leukemia (AML), metabolic dependencies are largely unexplored. We aimed to classify AML patients based on their metabolic landscape and map connections between metabolic and genomic profiles. Combined serum and urine metabolomics improved AML characterization compared with individual biofluid analysis. At intracellular level, AML displayed dysregulated amino acid, nucleotide, lipid, and bioenergetic metabolism. The integration of intracellular and biofluid metabolomics provided a map of alterations in the metabolism of polyamine, purine, keton bodies and polyunsaturated fatty acids and tricarboxylic acid cycle. The intracellular metabolome distinguished three AML clusters, correlating with distinct genomic profiles: NPM1-mutated(mut), chromatin/spliceosome-mut and TP53-mut/aneuploid AML that were confirmed by biofluid analysis. Interestingly, integrated genomic-metabolic profiles defined two subgroups of NPM1-mut AML. One was enriched for mutations in cohesin/DNA damage-related genes (NPM1/cohesin-mut AML) and showed increased serum choline + trimethylamine-N-oxide and leucine, higher mutation load, transcriptomic signatures of reduced inflammatory status and better ex-vivo response to EGFR and MET inhibition. The transcriptional differences of enzyme-encoding genes between NPM1/cohesin-mut and NPM1-mut allowed in silico modeling of intracellular metabolic perturbations. This approach predicted alterations in NAD and purine metabolism in NPM1/cohesin-mut AML that suggest potential vulnerabilities, worthy of being therapeutically explored.
- Published
- 2021
- Full Text
- View/download PDF
4. Chromothripsis in acute myeloid leukemia: Biological features and impact on survival
- Author
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Michele Cavo, Zdenek Racil, Viviana Guadagnuolo, Antonella Padella, Maria Chiara Fontana, Michael Steurer, Michael Doubek, Emanuela Ottaviani, Nicoletta Testoni, Giovanni Marconi, Marco Manfrini, Torsten Haferlach, Carmen Baldazzi, Stefania Paolini, Simona Soverini, Andrea Ghelli Luserna di Rorà, Vincenza Solli, Robert Kralovics, Anna Maria Ferrari, Eugenio Fonzi, Cristina Papayannidis, Eugenia Franchini, Giovanni Martinelli, Lukáš Semerád, Ilaria Iacobucci, Jelena D. Milosevic Feenstra, Giorgia Simonetti, Fontana, Maria Chiara, Marconi, Giovanni, Feenstra, Jelena D. Milosevic, Fonzi, Eugenio, Papayannidis, Cristina, Ghelli Luserna Di Rorá, Andrea, Padella, Antonella, Solli, Vincenza, Franchini, Eugenia, Ottaviani, Emanuela, Ferrari, Anna, Baldazzi, Carmen, Testoni, Nicoletta, Iacobucci, Ilaria, Soverini, Simona, Haferlach, Torsten, Guadagnuolo, Viviana, Semerad, Luka, Doubek, Michael, Steurer, Michael, Racil, Zdenek, Paolini, Stefania, Manfrini, Marco, Cavo, Michele, Simonetti, Giorgia, Kralovics, Robert, and Martinelli, Giovanni
- Subjects
0301 basic medicine ,Genome instability ,Oncology ,Adult ,Male ,medicine.medical_specialty ,NPM1 ,Cancer Research ,Adolescent ,Ring chromosome ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Young Adult ,Internal medicine ,Chromosome instability ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,Ring Chromosomes ,In Situ Hybridization, Fluorescence ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Chromothripsis ,Hematology ,business.industry ,Myeloid leukemia ,Adult Acute Myeloid Leukemia ,Middle Aged ,Prognosis ,3. Good health ,Chromosome Banding ,Leukemia, Myeloid, Acute ,030104 developmental biology ,Treatment Outcome ,Anesthesiology and Pain Medicine ,Mutation ,Female ,business ,Nucleophosmin - Abstract
Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study defines incidence of chromothripsis in 395 newly diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix??) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (p???=???0.002), ELN high risk (HR) (p?????0.001), lower white blood cell (WBC) count (p???=???0.040), TP53 loss, and/or mutations (p?????0.001) while FLT3 (p???=???0.025), and NPM1 (p???=???0.032) mutations were mutually exclusive with chromothripsis. Chromothripsis-positive patients showed a worse overall survival (OS) (p?????0.001) compared with HR patients (p???=???0.011) and a poor prognosis in a COX-HR optimal regression model. Chromothripsis presented the hallmarks of chromosome instability [i.e., TP53 alteration, 5q deletion, higher mean of copy number alteration (CNA), complex karyotype, alterations in DNA repair, and cell cycle] and focal deletions on chromosomes 4, 7, 12, 16, and 17. CBA. FISH showed that chromothripsis is associated with marker, derivative, and ring chromosomes. In conclusion, chromothripsis frequently occurs in AML (6.6%) and influences patient prognosis and disease biology.
- Published
- 2017
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