22 results on '"Bellosillo Paricio, Beatriz"'
Search Results
2. Machine Learning Improves Risk Stratification in Myelofibrosis: An Analysis of the Spanish Registry of Myelofibrosis
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Mosquera Orgueira, Adrián, Pérez Encinas, Manuel, Hernández Sánchez, Alberto, González Martínez, Teresa, Arellano Rodrigo, Eduardo, Martínez Elicegui, Javier, Villaverde Ramiro, Ángela, Raya, José María, Ayala, Rosa, Ferrer Marín, Francisca, Fox, María Laura, Velez, Patricia, Mora, Elvira, Xicoy, Blanca, Mata Vázquez, María Isabel, García Fortes, María, Angona, Anna, Cuevas, Beatriz, Senín, María Alicia, Ramírez Payer, Angel, Ramírez, María José, Pérez López, Raúl, González de Villambrosía, Sonia, Martínez Valverde, Clara, Gómez Casares, María Teresa, García Hernández, Carmen, Gasior, Mercedes, Bellosillo Paricio, Beatriz, Steegmann, Juan Luis, Álvarez Larrán, Alberto, Hernández Rivas, Jesús María, Hernández Boluda, Juan Carlos, The Spanish MPN Group (GEMFIN)., Institut Català de la Salut, [Mosquera-Orgueira A, Pérez-Encinas M] Hospital Clínico Universitario, Santiago de Compostela, Spain. [Hernández-Sánchez A, González-Martínez T, Martínez-Elicegui J] Hospital Clínico, Salamanca, Spain. [Arellano-Rodrigo E] Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. [Fox ML] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Intel·ligència artificial - Aplicacions a la medicina ,Pronòstic mèdic ,Mielofibrosi ,Immunology ,Myelofibrosis ,Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute [DISEASES] ,enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos [ENFERMEDADES] ,Cell Biology ,Hematology ,Prognosis ,Biochemistry ,Ciencias de la información::metodologías computacionales::algoritmos::inteligencia artificial::aprendizaje automático [CIENCIA DE LA INFORMACIÓN] ,neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda [ENFERMEDADES] ,Aprenentatge automàtic ,Machine learning ,Sang - Malalties ,Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders [DISEASES] ,Information Science::Computing Methodologies::Algorithms::Artificial Intelligence::Machine Learning [INFORMATION SCIENCE] - Abstract
Aprendizaje automático; Mielofibrosis Aprenentatge automàtic; Mielofibrosi Machine learning; Myelofibrosis Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical course. Allogeneic hematopoietic cell transplantation remains the only curative therapy, but its morbidity and mortality require careful candidate selection. Therefore, accurate disease risk prognostication is critical for treatment decision-making. We obtained registry data from patients diagnosed with MF in 60 Spanish institutions (N = 1386). These were randomly divided into a training set (80%) and a test set (20%). A machine learning (ML) technique (random forest) was used to model overall survival (OS) and leukemia-free survival (LFS) in the training set, and the results were validated in the test set. We derived the AIPSS-MF (Artificial Intelligence Prognostic Scoring System for Myelofibrosis) model, which was based on 8 clinical variables at diagnosis and achieved high accuracy in predicting OS (training set c-index, 0.750; test set c-index, 0.744) and LFS (training set c-index, 0.697; test set c-index, 0.703). No improvement was obtained with the inclusion of MPN driver mutations in the model. We were unable to adequately assess the potential benefit of including adverse cytogenetics or high-risk mutations due to the lack of these data in many patients. AIPSS-MF was superior to the IPSS regardless of MF subtype and age range and outperformed the MYSEC-PM in patients with secondary MF. In conclusion, we have developed a prediction model based exclusively on clinical variables that provides individualized prognostic estimates in patients with primary and secondary MF. The use of AIPSS-MF in combination with predictive models that incorporate genetic information may improve disease risk stratification.
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- 2023
3. In silico validation of RNA-Seq results can identify gene fusions with oncogenic potential in glioblastoma
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Hernández, Ainhoa, Muñoz-Mármol, Ana Maria, Esteve-Codina, Anna, Alameda, Francesc, Carrato, Cristina, Pineda, Estela, Arpí Lluciá, Oriol, Martinez-García, Maria, Mallo, Maria del Mar, Gut, Marta, Del Barco Berrón, Sonia, Gallego Rubio, Oscar, Dabad, Marc, Mesia, Carlos, Bellosillo Paricio, Beatriz, Domènech Viñolas, Marta, Vidal, Noemí, Aldecoa, Iban, de la Iglesia, Nuria, Balañá, Carmen, and Universitat Autònoma de Barcelona
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Multidisciplinary ,Oncogene Proteins, Fusion ,Molecular biology ,Carcinogenesis ,Glioma ,Molecular neuroscience ,CNS cancer ,Humans ,RNA ,Carcinogènesi ,RNA-Seq ,Gene Fusion ,Glioblastoma ,Microtubule-Associated Proteins ,Cancer ,Neuroscience - Abstract
RNA-Sequencing (RNA-Seq) can identify gene fusions in tumors, but not all these fusions have functional consequences. Using multiple data bases, we have performed an in silico analysis of fusions detected by RNA-Seq in tumor samples from 139 newly diagnosed glioblastoma patients to identify in-frame fusions with predictable oncogenic potential. Among 61 samples with fusions, there were 103 different fusions, involving 167 different genes, including 20 known oncogenes or tumor suppressor genes (TSGs), 16 associated with cancer but not oncogenes or TSGs, and 32 not associated with cancer but previously shown to be involved in fusions in gliomas. After selecting in-frame fusions able to produce a protein product and running Oncofuse, we identified 30 fusions with predictable oncogenic potential and classified them into four non-overlapping categories: six previously described in cancer; six involving an oncogene or TSG; four predicted by Oncofuse to have oncogenic potential; and 14 other in-frame fusions. Only 24 patients harbored one or more of these 30 fusions, and only two fusions were present in more than one patient: FGFR3::TACC3 and EGFR::SEPTIN14. This in silico study provides a good starting point for the identification of gene fusions with functional consequences in the pathogenesis or treatment of glioblastoma.
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- 2022
4. A Standardized Liquid Biopsy Preanalytical Protocol for Downstream Circulating-Free DNA Applications
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Earl, Julie, primary, Calabuig-Fariñas, Silvia, primary, Sarasquete, María Eugenia, primary, Muinelo Romay, Laura, primary, Lopez-Tarruella, Sara, primary, Bellosillo Paricio, Beatriz, primary, Rodríguez, Marta, primary, Valencia Leoz, Karmele, primary, Dueñas Porto, Marta, primary, Tarazona, Noelia, primary, Hernandez Losa, Javier, primary, and Toledo, Rodrigo Almeida, primary
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- 2022
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5. Evaluating the Potential of Polygenic Risk Score to Improve Colorectal Cancer Screening
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Arnau Collell, Coral, Díez Villanueva, Anna, Bellosillo Paricio, Beatriz, Augé, Josep M., Muñoz, Jenifer, Guinó, Elisabet, Moreira, Leticia, Serradesanferm, Anna, Pozo, Àngels, Torà Rocamora, Isabel, Bonjoch, Laia, Ibañez Sanz, Gemma, Obon Santacana, Mireia, Moratalla Navarro, Ferran, Sanz Pamplona, Rebeca, Márquez Márquez, Carmen, Rueda Miret, Rebeca, Pérez Berbegal, Rocio, Piquer Velasco, Gabriel, Hernández Rodríguez, Cristina, Grau, Jaume, Castells, Antoni, Borràs, Josep Maria, Bessa i Caserras, Xavier, Moreno, Víctor, Castellví Bel, Sergi, and CRIPREV consortium
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Male ,Multifactorial Inheritance ,Factors de risc en les malalties ,Medical screening ,Risk factors in diseases ,Epidemiology ,Colonoscopy ,Colorectal cancer ,Còlon--Càncer ,Cribratge ,Oncology ,Càncer colorectal ,Risk Factors ,Occult Blood ,Marcadors bioquímics ,Mortalitat ,Humans ,Mass Screening ,Female ,Colorectal Neoplasms ,Early Detection of Cancer - Abstract
Background: Colorectal cancer has high incidence and associated mortality worldwide. Screening programs are recommended for men and women over 50. Intermediate screens such as fecal immunochemical testing (FIT) select patients for colonoscopy with suboptimal sensitivity. Additional biomarkers could improve the current scenario. Methods: We included 2,893 individuals with a positive FIT test. They were classified as cases when a high-risk lesion for colorectal cancer was detected after colonoscopy, whereas the control group comprised individuals with low-risk or no lesions. 65 colorectal cancer risk genetic variants were genotyped. Polygenic risk score (PRS) and additive models for risk prediction incorporating sex, age, FIT value, and PRS were generated. Results: Risk score was higher in cases compared with controls [per allele OR = 1.04; 95% confidence interval (CI), 1.02–1.06; P < 0.0001]. A 2-fold increase in colorectal cancer risk was observed for subjects in the highest decile of risk alleles (≥65), compared with those in the first decile (≤54; OR = 2.22; 95% CI, 1.59–3.12; P < 0.0001). The model combining sex, age, FIT value, and PRS reached the highest accuracy for identifying patients with a high-risk lesion [cross-validated area under the ROC curve (AUROC): 0.64; 95% CI, 0.62–0.66]. Conclusions: This is the first investigation analyzing PRS in a two-step colorectal cancer screening program. PRS could improve current colorectal cancer screening, most likely for higher at-risk subgroups. However, its capacity is limited to predict colorectal cancer risk status and should be complemented by additional biomarkers. Impact: PRS has capacity for risk stratification of colorectal cancer suggesting its potential for optimizing screening strategies alongside with other biomarkers.
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- 2022
6. Evaluation of four prognostic indices in follicular lymphoma treated in first line with immunochemotherapy
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Rodríguez-Sevilla, Juan José, Fernández Rodríguez, M. Concepción, Bento, Leyre, Díez-Feijóo, Ramón, Felipe Pinzon, Sergio, Gibert Fernandez, Joan 1988, Fernández-Ibarrondo, Lierni, Lafuente, Marta, Ferrer Del Alamo, Ana, Sánchez González, Blanca, Gimeno Vázquez, Eva, Sainz, Juan, Ramos-Asensio, Rafael, García, Juan Fernando, Colomo Saperas, Luis Alberto, Bellosillo Paricio, Beatriz, Gutierrez, Antonio, and Salar Silvestre, Antonio
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Immunoteràpia ,Limfomes -- Tractament ,Genètica - Abstract
[AHEAD] Data de publicació electrónica: 19-10-2022 Several clinical risk models have been proposed to predict outcome in follicular lymphoma (FL). The development of Next Generation Sequencing (NGS) technologies has allowed the integration of somatic gene mutations in clinical scores to build genotyped-based risk models, such as m7-FLIPI. We explored four clinical or clinicogenetic risk models in patients with symptomatic FL who received frontline immunochemotherapy. Out of 191 patients with FL grade 1-3a, 109 were successfully genotyped. Treatment consisted on rituximab (R) plus CVP/CHOP (72.5%) or R-bendamustine (R-B) (27.5%). The proportion of cases classified as high-risk in FLIPI, FLIPI-2, PRIMA-PI or m7-FLIPI were 39.3%, 14%, 30.3%, 22%, respectively. No case with low-intermediate FLIPI was upgraded in m7-FLIPI, but 18 out of 42 higher-risk patients in FLIPI were downgraded to low-risk m7-FLIPI. Sensitivity and specificity for the prediction of POD24 was highest for FLIPI. The discrimination for progression free survival (PFS) and overall survival (OS) was best for FLIPI (c-index: 0.644 and 0.727, respectively). When analyzed only R-B patients, m7-FLIPI had higher discrimination for PFS and OS. Thus, FLIPI remains as the clinical risk score with higher discrimination in advanced FL patients treated with immunochemotherapy, but the performance of m7-FLIPI should be further investigated in patients treated with R-B.
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- 2022
7. Genomic characterization of patients with polycythemia vera developing resistance to hydroxyurea
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Alvarez-Larrán, Alberto, Díaz-González, Alvaro, Such, Esperanza, Mora, Elvira, Andrade-Campos, Marcio, García-Hernández, Carmen, Gómez-Casares, Maria-Teresa, García-Gutiérrez, Valentín, Carreño-Tarragona, Gonzalo, Garrote, Marta, Fernández-Ibarrondo, Lierni, Cervera, José, Bellosillo Paricio, Beatriz, Cervantes, Francisco, Hernández-Boluda, Juan Carlos, and MPN Spanish Group (GEMFIN)
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Cancer Research ,Letter ,Trastorns mieloproliferatius ,business.industry ,Policitèmia ,Antineoplastic Agents ,Genomics ,Hematology ,Prognosis ,medicine.disease ,Bioinformatics ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Myeloproliferative disease ,Polycythemia vera ,Oncology ,Drug Resistance, Neoplasm ,Biomarkers, Tumor ,medicine ,Humans ,Hydroxyurea ,business ,Polycythemia Vera ,Cancer genetics ,Genètica - Abstract
Data de publicació electrónica: 05-05-2020
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- 2020
8. HER-Family Ligands Promote Acquired Resistance to Trastuzumab in Gastric Cancer
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Sampera Borràs, Aïda, 1990, Sánchez-Martín, Francisco Javier, Arpí Llucià, Oriol, Visa Turmo, Laura, Iglesias Coma, Mar, Menéndez, Silvia, Gaye, Élisabeth, Dalmases Massegú, Alba, 1982, Clavé Safont, Sergi, Gelabert-Baldrich, Mariona, Tuxen Poulsen, Thomas, Kragh, Michael, Bellosillo Paricio, Beatriz, Albanell Mestres, Joan, Rovira Guerín, Ana, and Montagut Viladot, Clara
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Male ,0301 basic medicine ,MAPK/ERK pathway ,Cancer Research ,MAP Kinase Signaling System ,Receptor, ErbB-2 ,Drug resistance ,Mice ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Stomach Neoplasms ,Trastuzumab ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm ,skin and connective tissue diseases ,Receptor ,neoplasms ,PI3K/AKT/mTOR pathway ,business.industry ,TOR Serine-Threonine Kinases ,Cancer ,medicine.disease ,Up-Regulation ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Aparell digestiu -- Càncer -- Tractament ,Oncology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,business ,medicine.drug - Abstract
Despite the clinical benefit of trastuzumab, eventually all HER2-amplified gastric cancer tumors develop drug resistance. We aimed to identify molecular mechanisms of acquired resistance to trastuzumab in gastric cancer by using well-established cell line–based preclinical models, as well as samples from patients with HER2-positive gastric cancer treated with trastuzumab. We studied trastuzumab resistance in NCI-N87 and OE19, two gastric cancer cell lines that overexpress HER2 receptor and are trastuzumab sensitive. Differences at protein, DNA, and RNA levels between the parental and resistant cells were characterized and functional studies were performed. Paired pre- and post-trastuzumab blood and tissue samples from patients with gastric cancer treated with trastuzumab were analyzed. We found that resistant cells were associated with increased activation of MAPK/ERK and PI3K/mTOR pathways driven by SRC activation. Upstream, resistant cells showed increased coexpression of multiple HER-family ligands that allowed for compensatory activation of alternative HER receptors upon HER2 blockade. Simultaneous inhibition of EGFR, HER2, and HER3 by the novel antibody mixture, Pan-HER, effectively reverted trastuzumab resistance in vitro and in vivo. Similarly, an increase in HER-family ligands was observed in serum and tumor from patients with gastric cancer after trastuzumab therapy. We propose that trastuzumab resistance in gastric cancer is mediated by HER-family ligand upregulation that allows a compensatory activation of HER receptors and maintains downstream signaling activation despite trastuzumab therapy. Resistance is reverted by simultaneous inhibition of EGFR, HER2, and HER3, thereby revealing a potential therapeutic strategy to overcome trastuzumab resistance in patients with gastric cancer.
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- 2019
9. Among classic myeloproliferative neoplasms, essential thrombocythemia is associated with the greatest risk of venous thromboembolism during COVID-19
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Barbui, Tiziano, De Stefano, Valerio, Alvarez-Larran, Alberto, Iurlo, Alessandra, Masciulli, Arianna, Carobbio, Alessandra, Ghirardi, Arianna, Ferrari, Alberto, Cancelli, Valeria, Elli, Elena Maria, Andrade-Campos, Marcio Miguel, Kabat, Mercedes Gasior, Kiladjian, Jean-Jaques, Palandri, Francesca, Benevolo, Giulia, Garcia-Gutierrez, Valentin, Fox, Maria Laura, Foncillas, Maria Angeles, Morcillo, Carmen Montoya, Rumi, Elisa, Osorio, Santiago, Papadopoulos, Petros, Bonifacio, Massimiliano, Quiroz Cervantes, Keina, Serrano, Miguel Sagues, Carreño-Tarragona, Gonzalo, Sobas, Marta Anna, Lunghi, Francesca, Patriarca, Andrea, Elorza, Begoña Navas, Angona, Anna, Mazo, Elena Magro, Koschmieder, Steffen, Carli, Giuseppe, Cuevas, Beatriz, Hernandez-Boluda, Juan Carlos, Abadia, Emma Lopez, Xicoy, Blanca, Guglielmelli, Paola, Garrote, Marta, Cattaneo, Daniele, Daffini, Rosa, Cavalca, Fabrizio, Bellosillo Paricio, Beatriz, Benajiba, Lina, Curto-Garcia, Natalia, Bellini, Marta, Betti, Silvia, Harrison, Claire, Rambaldi, Alessandro, Vannucchi, Alessandro Maria, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Barbui T, Masciulli A, Carobbio A] FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy. [De Stefano V] Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University, Fondazione Policlinico 'A. Gemelli' IRCCS, Rome, Italy. [Alvarez-Larran A] Hospital Clinic de Barcelona, Barcelona, Spain. [Iurlo A] Hematology Division, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy. [Fox ML] Servei d’Hematologia, Vall d’Hebron Institute of Oncology (VHIO), Barcelona Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Male ,COVID-19 (Malaltia) - Factors de risc ,030204 cardiovascular system & hematology ,Gastroenterology ,Cohort Studies ,Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores] ,Myeloproliferative disease ,0302 clinical medicine ,Polycythemia vera ,Antithrombotic ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Cumulative incidence ,Trombosi ,enfermedades cardiovasculares::enfermedades vasculares::embolia y trombosis::tromboembolia::tromboembolia venosa [ENFERMEDADES] ,Aged, 80 and over ,Univariate analysis ,Mortality rate ,Cardiovascular Diseases::Vascular Diseases::Embolism and Thrombosis::Thromboembolism::Venous Thromboembolism [DISEASES] ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,Hematology ,Venous Thromboembolism ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Thrombosis ,3. Good health ,Europe ,Myeloid leukemia ,Oncology ,030220 oncology & carcinogenesis ,Infectious diseases ,Female ,Thrombocythemia, Essential ,medicine.medical_specialty ,Leucèmia mieloide ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Myelofibrosis ,Pandemics ,Tromboembolisme ,Aged ,Retrospective Studies ,Myeloproliferative Disorders ,Essential thrombocythemia ,business.industry ,SARS-CoV-2 ,COVID-19 ,medicine.disease ,Risk factors ,business ,Bone Marrow Neoplasms ,Other subheadings::Other subheadings::/complications [Other subheadings] - Abstract
Blood cancer journal 11(2), 21 (2021). doi:10.1038/s41408-021-00417-3, Published by Nature Publishing Group, London [u.a.]
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- 2021
10. Long-term follow-up of recovered MPN patients with COVID-19
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Barbui, Tiziano, Iurlo, Alessandra, Masciulli, Arianna, Carobbio, Alessandra, Ghirardi, Arianna, Rossi, Giuseppe, Harrison, Claire, Alvarez-Larran, Alberto, Elli, Elena María, Kiladjian, Jean-Jaques, Gasior Kabat, Mercedes, Marin Sanchez, Alberto, Palandri, Francesca, Andrade-Campos, Marcio Miguel, Vannucchi, Alessandro Maria, Carreño-Tarragona, Gonzalo, Papadopoulos, Petros, Quiroz Cervantes, Keina, Foncillas, Maria Angeles, Fox, Maria Laura, Sagues Serrano, Miguel, Rumi, Elisa, Osorio, Santiago, Benevolo, Giulia, Patriarca, Andrea, Navas Elorza, Begoña, Garcia-Gutierrez, Valentín, Magro Mazo, Elena, Lunghi, Francesca, Bonifacio, Massimiliano, De Stefano, Valerio, Hernandez-Boluda, Juan Carlos, Lopez Abadia, Emma, Angona, Anna, Xicoy Cirici, Blanca, Ruggeri, Marco, Koschmieder, Steffen, Sobas, Marta Anna, Cuevas, Beatriz, Cattaneo, Daniele, Daffini, Rosa, Bellini, Marta, Curto-Garcia, Natalia, Garrote, Marta, Cavalca, Fabrizio, Benajiba, Lina, Bellosillo Paricio, Beatriz, Guglielmelli, Paola, Borsani, O., Betti, Silvia, Salmoiraghi, Silvia, Rambaldi, Alessandro, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Barbui T, Masciulli A, Carobbio A, Ghirardi A] FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy. [Iurlo A] Hematology Division, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy. [Rossi G] Spedali Civili, Brescia, Italy. [Fox ML] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Myeloid ,Male ,Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores] ,Myeloproliferative disease ,Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders [DISEASES] ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Otros calificadores::/terapia [Otros calificadores] ,RC254-282 ,Aged, 80 and over ,Leukemia ,Lymphoma, Non-Hodgkin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,Hematology ,Middle Aged ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Treatment Outcome ,Oncology ,Infectious diseases ,Female ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Long term follow up ,MEDLINE ,enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos [ENFERMEDADES] ,Myeloproliferative Disorders ,COVID-19 (Malaltia) - Tractament ,Internal medicine ,Correspondence ,COVID-19 - complications ,medicine ,Humans ,Aged ,business.industry ,SARS-CoV-2 ,Trastorns mieloproliferatius - Complicacions ,COVID-19 ,COVID-19 - mortality ,Other subheadings::/therapy [Other subheadings] ,medicine.disease ,Lymphoma ,Avaluació de resultats (Assistència sanitària) ,business ,Other subheadings::Other subheadings::/complications [Other subheadings] ,Follow-Up Studies - Abstract
Blood cancer journal 11(6), 115 (2021). doi:10.1038/s41408-021-00509-0, Published by Nature Publishing Group, London [u.a.]
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- 2021
11. The risk of thrombosis in essential thrombocythemia is associated with the type of CALR mutation: A multicentre collaborative study
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Pérez Encinas, Manuel M., primary, Sobas, Marta, additional, Gómez‐Casares, María Teresa, additional, Abuin Blanco, Aitor, additional, Noya Pereira, María Soledad, additional, Raya, José María, additional, Andrade‐Campos, Marcio M., additional, Álvarez Larrán, Alberto, additional, Lewandowski, Krzysztof, additional, Łukasz, Szukalski, additional, Hernández Boluda, Juan Carlos, additional, Ferrer‐Marín, Francisca, additional, Fox, María Laura, additional, Gołos, Aleksandra, additional, Gasior Kabat, Mercedes, additional, Magro Mazo, Elena, additional, Czyż, Anna, additional, Martín Martín, Alejandro, additional, Bellosillo Paricio, Beatriz, additional, Quinteiro García, Celsa, additional, González Martín, Jesús María, additional, and Stuckey, Ruth, additional
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- 2020
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12. Impact of human papilloma virus in patients with oral and oropharyngeal squamous cell carcinomas
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Valls-Ontañón, Adaia, primary, Hernández-Losa, Javier, additional, de Haro, Rosa Somoza Lopez, additional, Bellosillo-Paricio, Beatriz, additional, y Cajal, Santiago Ramón, additional, Bescós-Atín, Coro, additional, Munill-Ferrer, Montserrat, additional, and Alberola-Ferranti, Margarita, additional
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- 2019
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13. Impacto del virus papiloma humano en pacientes afectos de carcinoma escamoso de cavidad oral y orofaringe
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Valls-Ontañón, Adaia, primary, Hernández-Losa, Javier, additional, Somoza Lopez de Haro, Rosa, additional, Bellosillo-Paricio, Beatriz, additional, Ramón y Cajal, Santiago, additional, Bescós-Atín, Coro, additional, Munill-Ferrer, Montserrat, additional, and Alberola-Ferranti, Margarita, additional
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- 2019
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14. The risk of thrombosis in essential thrombocythemia is associated with the type of CALR mutation: A multicentre collaborative study.
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Pérez Encinas, Manuel M., Sobas, Marta, Gómez‐Casares, María Teresa, Abuin Blanco, Aitor, Noya Pereira, María Soledad, Raya, José María, Andrade‐Campos, Marcio M., Álvarez Larrán, Alberto, Lewandowski, Krzysztof, Łukasz, Szukalski, Hernández Boluda, Juan Carlos, Ferrer‐Marín, Francisca, Fox, María Laura, Gołos, Aleksandra, Gasior Kabat, Mercedes, Magro Mazo, Elena, Czyż, Anna, Martín Martín, Alejandro, Bellosillo Paricio, Beatriz, and Quinteiro García, Celsa
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THROMBOCYTOSIS ,THROMBOSIS ,PROGNOSIS ,VENOUS thrombosis ,DIAGNOSIS - Abstract
Objectives: In patients with essential thrombocythemia (ET), after the JAK2V617F driver mutation, mutations in CALR are common (classified as type 1, 52‐bp deletion or type 2, 5‐bp insertion). CALR mutations have generally been associated with a lower risk of thrombosis. This study aimed to confirm the impact of CALR mutation type on thrombotic risk. Methods: We retrospectively investigated 983 ET patients diagnosed in Spanish and Polish hospitals. Results: With 7.5 years of median follow‐up from diagnosis, 155 patients (15.8%) had one or more thrombotic event. The 5‐year thrombosis‐free survival (TFS) rate was 83.8%, 91.6% and 93.9% for the JAK2V617F, CALR‐type 1 and CALR‐type 2 groups, respectively (P =.002). Comparing CALR‐type 1 and CALR‐type 2 groups, TFS for venous thrombosis was lower in CALR‐type 1 (P =.046), with no difference in TFS for arterial thrombosis observed. The cumulative incidence of thrombosis was significantly different comparing JAK2V617F vs CALR‐type 2 groups but not JAK2V617F vs CALR‐type 1 groups. Moreover, CALR‐type 2 mutation was a statistically significant protective factor for thrombosis with respect to JAK2V617F in multivariate logistic regression (OR: 0.45, P =.04) adjusted by age. Conclusions: Our results suggest that CALR mutation type has prognostic value for the stratification of thrombotic risk in ET patients. [ABSTRACT FROM AUTHOR]
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- 2021
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15. Molecular analysis of peripheral lung adenocarcinoma in brush cytology obtained by endobronchial ultrasound plus fluoroscopy-guided
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Martin Ontiyuelo, Clara, primary, Pijuan Andujar, Lara, additional, Chalela Rengifo, Roberto, additional, Albero Gonzalez, Raquel, additional, Bellosillo Paricio, Beatriz, additional, Dalmases Massegu, Alba, additional, Longaron Rozalen, Raquel, additional, Curull Serrano, Victor, additional, and Sanchez Font, Albert, additional
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- 2018
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16. Molecular characterisation of triple negative essential thrombocythaemia patients by platelet analysis and targeted sequencing
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Angona, A, Fernández-Rodríguez, C, Alvarez-Larrán, A, Camacho, L, Longarón, R, Torres, E, Pairet, S, Besses, C, Bellosillo Paricio, Beatriz, and Universitat Autònoma de Barcelona
- Subjects
Adult ,Blood Platelets ,Male ,medicine.medical_specialty ,Adolescent ,Trombocitèmia ,Biology ,Real-Time Polymerase Chain Reaction ,Cohort Studies ,Fusion gene ,Transcriptome ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Molecular diagnostic techniques ,Plaquetes sanguínies -- Trastorns ,Platelet ,Child ,Letter to the Editor ,Triple negative ,Aged ,Aged, 80 and over ,Hematology ,Translational biology ,High-Throughput Nucleotide Sequencing ,Sequence Analysis, DNA ,Janus Kinase 2 ,Middle Aged ,Real-time polymerase chain reaction ,Molecular Diagnostic Techniques ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Female ,Calreticulin ,Receptors, Thrombopoietin ,Polymorphism, Restriction Fragment Length ,Thrombocythemia, Essential ,030215 immunology - Abstract
Essential thrombocythaemia (ET) is a myeloproliferative neoplasm(MPN) characterised by megakaryocyte hyperplasia and thrombo-cytosis. From the genetic perspective, ET patients harbourmutations inJAK2(50–60%),CALR(15–30%) andMPL(1–5%) genes. This study was supported in part by grants from ISCIII and Spanish Ministry of Health, PI13/00557, PI13/00393, RD12/0036/0010, PT13/0010/0005, 2014SGR567 and the Xarxa de Banc de Tumors de Catalunya.
- Published
- 2016
17. Bases moleculars de la leucèmia limfàtica crònica i la seva teràpia
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Colomer i Pujol, Dolors, Pons, Gabriel, Gil i Santano, Joan, Bellosillo Paricio, Beatriz, and Universitat de Barcelona
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Leukemia ,Leucèmia ,Therapeutics ,Terapèutica - Abstract
La leucèmia limfàtica crònica de tipus B (LLC-B) representa el 30-40% de les leucèmies en els països occidentals i es caracteritza per l'acumulació de limfòcits B-CD5*, que expressen uns alts nivells de Bcl-2. Anàlegs a les purines i inhibidors de la topoisomerasa II, han estat utilitzats com a agents quimioterapèutics en el tractament de la LLC-B. S'ha observat que tot ells actuen induint l'apoptosi de les cèl·lules de la LLC-B a través de l'activació de les caspases. També s'ha observat que l'aspirina i el salicilat poden induir l'apoptosi de les cèl·lules de la LLC-B mitjançant l'activació de les caspases i per mecanismes independents de la ciclooxigenasa.
- Published
- 1999
18. Improving molecular diagnosis in myeloid neoplasms : The role of cell-free DNA
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García Gisbert, Nieves, 1994, Bellosillo Paricio, Beatriz, Besses Raebel, C. (Carles), Calvo González, Xavier, and Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut.
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616.4 - Abstract
Myeloid malignancies are clonal diseases originated in myeloid hematopoietic stem cells that are frequently initiated by somatic mutations. The detection of genetic alterations has considerably improved the diagnostic accuracy in myeloid neoplasms, however multiple aspects should be further improved in the diagnostic and classification tools that are used in clinical practice. The main goal of the research projects presented in this thesis is to improve the accuracy of the diagnosis and classification of myeloid malignancies, focused on myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). We explored the role of cell free DNA (cfDNA) analysis as a new non-invasive diagnostic tool in MPN and MDS patients and detected an equivalent mutational profile in paired samples of cfDNA and tumoral cells. On the other hand, we compared the clinical, genomic, and immunophenotypic features of a series of oligomonocytic CMML (OM-CMML) and overt CMML and observed similar characteristics supporting the consideration of OM-CMML as a distinctive subtype of CMML. Finally, we assessed if saliva samples and CD3+ lymphocytes were a suitable source of germline DNA in MPN patients, and found that the use CD3+ lymphocytes was a better option for germline DNA obtention than saliva samples, which were frequently contaminated with tumoral cells. Las neoplasias mieloides son enfermedades clonales que se originan en las células madre hematopoyéticas mieloides y son iniciadas generalmente por mutaciones somáticas. La detección de estas alteraciones genéticas ha mejorado considerablemente la precisión diagnóstica en las neoplasias mieloides, sin embargo, aún se deben mejorar múltiples aspectos en las herramientas de diagnóstico y clasificación que se utilizan en la práctica clínica. El objetivo principal de los estudios presentados en esta tesis es mejorar la precisión del diagnóstico y clasificación de las neoplasias mieloides, en concreto en neoplasias mieloproliferativas (NMP), síndromes mielodisplásicos (SMD) y leucemia mielomonocítica crónica (LMMC). Hemos explorado el papel del análisis de ADN libre circulante (cfDNA) como una nueva herramienta diagnóstica no invasiva en pacientes con NMP y SMD, y hemos detectado un perfil mutacional equivalente en muestras pareadas de cfDNA y células tumorales. Por otro lado, comparamos las características clínicas, genómicas e inmunofenotípicas de una serie de LMMC oligomonocítica (OM-CMML) y LMMC clásica y observamos características similares entre ambos grupos, lo que apoya la consideración de OM-CMML como un subtipo de LMMC. Finalmente, evaluamos si las muestras de saliva y los linfocitos CD3 + eran una fuente adecuada de ADN de línea germinal en pacientes con NMP, y observamos que el uso de linfocitos CD3+ era una mejor opción para la obtención de ADN germinal que las muestras de saliva, que estaban contaminadas en su mayoría con células tumorales.
- Published
- 2022
19. Aplicación de la secuenciación masiva en el diagnóstico y manejo del linfoma folicular
- Author
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Fernández Rodríguez, Mª Concepción, Salar Silvestre, Antonio, Bellosillo Paricio, Beatriz, and Bassols Teixidó, Anna Maria
- Subjects
Limfoma fol·licular ,Linfoma folicular ,Seqüenciació ,Secuenciación ,Sequencing ,Ciències de la Salut ,Follicular lymphoma - Abstract
El limfoma fol·licular (LF) és el segon linfoma no-Hodgkin més freqüent, amb característiques clíniques i moleculars molt heterogènies. Encara que es caracteritza per un curs clínic en general indolent, al menys un 20-30% dels pacients no responen o bé progressen dintre dels primers 2 anys de tractament, presentanty un especial mal pronòstic. Malgrat això, a dia d’avui no hi ha eines que permetin predir el pronòstic dels pacients al diagnòstic, el que resulta necessari per ajustar el seu maneig i tractament d’acord al risc. L’objectiu d’aquest estudi és analitzar el perfil genètic dels pacients amb LF per tal d’identificar correlacions clíniques i pronòstiques, estudiant les diferències en funció del tractament administrat. Per adreçar aquests objectius, es van analitzar mitjançant secuenciació massiva les mutacions genètiques en 64 gens relacionats amb el LF, sobre una sèrie de 109 pacients provinents de 3 hospitals nacionals. Tots els pacients inclosos a l’estudi presentaven mutacions relacionades amb la malaltia, mostrant una predominància d’alteracions en les vies de senyalització epigenètica i transcripcional, amb una elevada heterogeneïtat d’alteracions implicades en altres vies, sense detectar patrons o comutacions que identifiquin subgrups. Els gens que presenten alteracions concretes recurrents mostraven un impacte pronòstic més definit. Els pacients amb mutacions d’STAT6 Asp419 presenten mal pronòstic i aquells amb la mutació de CTSS Tyr132Asp mostraven una supervivència molt superior i absència d’afectació de la medul·la óssia, amb possibles implicacions en el maneig i el tractament. Els pacients amb mutacions en el gen ARID1A i aquells amb mutacions en els gens que codifiquen per a les proteïnes del complex mTORC1, van mostrar una millor supervivència en els casos sota teràpia amb rituximab-bendamustina, pel que la detecció d’aquestes alteracions al diagnòstic del LF podria ser rellevant en l’elecció del tractament. El linfoma folicular (LF) es el segundo linfoma no-Hodgkin más frecuente, con características clínicas y moleculares muy heterogéneas. Aunque se caracteriza por un curso clínico en general indolente, al menos un 20-30% de los pacientes no responden o bien progresan en los primeros 2 años de tratamiento, presentando un especial mal pronóstico. Sin embargo, a día de hoy no existen herramientas que permitan predecir el pronóstico de los pacientes al diagnóstico, lo que resulta necesario para ajustar su manejo y tratamiento de acuerdo al riesgo. El objetivo de este estudio es analizar el perfil genético de los pacientes con LF para identificar correlaciones clínicas y pronósticas, estudiando las diferencias en función del tratamiento administrado. Para ello, se analizaron mediante secuenciación masiva las mutaciones genéticas en 64 genes relacionados con el LF, sobre una serie de 109 pacientes provenientes de 3 hospitales nacionales. Todos los pacientes incluidos en el estudio presentaron mutaciones relacionadas con la enfermedad, mostrando una predominancia de alteraciones en las vías de señalización epigenética y transcripcional, con una elevada heterogeneidad de alteraciones implicadas en otras vías, sin detectarse patrones o coexistencias que identifiquen subgrupos. Los genes que presentaban alteraciones concretas recurrentes mostraban un impacto pronóstico más definido. Los pacientes con mutaciones de STAT6 Asp419 presentaban mal pronóstico y aquellos con la mutación de CTSS Tyr132Asp mostraban una supervivencia muy superior y ausencia de afectación de la médula ósea, con potenciales implicaciones en el manejo y el tratamiento. Los pacientes con mutaciones en el gen ARID1A y aquellos con mutaciones en los genes que codifican para las proteínas del complejo mTORC1, mostraron una mejor supervivencia en los casos bajo terapia con rituximab-bendamustina, por lo que la detección de estas alteraciones al diagnóstico del LF podría ser relevante en la elección del tratamiento. Follicular lymphoma (LF) is the second most common non-Hodgkin’s lymphoma, with very heterogeneous clinical and molecular features. Although it is characterized by a generally indolent clinical course, at least 20-30% of patients do not respond or progress during the first 2 years after treatment, presenting a special poor prognosis. However, there are no tools to predict the prognosis of patients at diagnosis, which is necessary to adjust their management and treatment according to their risk. The aim of this study was to analyze the genetic profile of patients with LF to identify clinical and prognostic correlations, studying the differences according on the treatment administered. To this end, genetic mutations in 64 LF-related genes were analyzed by next generation sequencing on a series of 109 patients from 3 national hospitals. All patients included in the study presented mutations related to the disease, showing a predominance of alterations in the epigenetic and transcriptional signaling pathways, with a high heterogeneity of alterations involved in other pathways, without detecting patterns or coexistences that identify subgroups. Genes with recurrent specific alterations showed a more definite prognostic impact. Patients with STAT6 Asp419 mutations had a poor prognosis and those with the CTSSTyr132Asp mutation showed much better survival and no bone marrow involvement, with potential implications for management and treatment. Patients with mutations in the ARID1A gene and those with mutations in the genes encoding mTORC1 complex proteins showed better survival in cases under rituximab-bendamustine therapy, so the detection of these alterations at the diagnosis of LF could be relevant in the choice of treatment. Universitat Autònoma de Barcelona. Programa de Doctorat en Bioquímica, Biologia Molecular i Biomedicina
- Published
- 2021
20. Valor diagnòstic i pronòstic de l'anàlisi genotípica als limfomes cutanis primaris utilitzant els protocols de reacció en cadena de la polimerasa BIOMED-2
- Author
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López Aventín, Daniel, Gallardo, F. (Fernando), Bellosillo Paricio, Beatriz, Pujol Vallverdú, Ramón M., and Gallardo, Fernando
- Subjects
Linfoma cutáneo ,Limfoma cutani ,Cutaneous lymphoma ,Clonalitat ,Clonalidad ,616.5 ,Ciències de la Salut ,Clonality - Abstract
Introducció i Objectius: Els protocols estandarditzats de reacció en cadena de la polimerasa (PCR) BIOMED-2 són àmpliament utilitzats per a la detecció de poblacions clonals de cèl·lules T/B i representen una eina diagnòstica important en l’avaluació dels limfomes cutanis (LC). L’objectiu d’aquest estudi va ser avaluar el valor diagnòstic i pronòstic dels resultats de l’anàlisi genotípica obtinguts a través d’aquestes tècniques en la pràctica clínica diària. Mètodes: Tres-centes seixanta mostres de pell van ser revisades retrospectivament de 149 pacients diagnosticats segons la classificació WHO-EORTC com: 114 limfomes cutanis de cèl·lules T (LCCT) i 35 limfomes cutanis de cèl·lules B (LCCB). Dues-centes quaranta-nou biòpsies de 180 pacients amb infiltrats limfoides cutanis benignes van servir de controls. De tots els casos es va estudiar teixit fixat en formol i inclòs en parafina, també es van analitzar mostres de sang perifèrica de 179 pacients. Es van avaluar els reordenaments gènics del receptor de la cèl·lula T i de la immunoglobulina mitjançant els protocols de PCR BIOMED-2. La mediana del seguiment va ser de 75,7 i de 45,9 mesos als subjectes amb LC i control, respectivament. Resultats: El protocol de PCR BIOMED-2 és un mètode útil per distingir LCCT d’infiltrats T cutanis benignes amb alta sensibilitat (89,4%) i significativa especificitat (81,5%). També proporciona dades valuoses en el diagnòstic particularment difícil de la micosi fungoide (MF) en estadi inicial que pot imitar dermatosis inflamatòries comunes (sensibilitat = 89,1% i especificitat = 85,5%). L’anàlisi de les recombinacions d’IGH (VH-JH) també ha estat útil per diferenciar LCCB d’infiltrats B cutanis benignes amb elevada sensibilitat (85,7%) i especificitat raonable (82,4%). L’addició d’IGK a l’avaluació d’IGH va augmentar la taxa de detecció de clonalitat del 85,7% al 100%, malgrat, disminuir l’especificitat. Es va identificar heterogeneïtat clonal entre biòpsies seqüencials o de diferents localitzacions en el 14,3% dels LCCT i l’11,8% dels LCCB. La detecció d’un clon T idèntic a la pell i a la sang perifèrica s’associa amb pitjor supervivència global i específica de la malaltia als pacients amb LC primaris, LCCT i MF/síndrome de Sézary. Conclusions: El protocol de PCR BIOMED-2 ha demostrat ser una estratègia de diagnòstic útil combinat amb les troballes clíniques, histològiques i immunofenotípiques, amb algunes implicacions pronòstiques, per estudiar pacients amb proliferacions limfoides cutànies. Introducción y Objetivos: Los protocolos estandarizados de reacción en cadena de la polimerasa (PCR) BIOMED-2 son ampliamente utilizados para la detección de poblaciones clonales de células T/B y representan una herramienta diagnóstica importante en la evaluación de los linfomas cutáneos (LC). El objetivo de este estudio fue evaluar el valor diagnóstico y pronóstico de los resultados del análisis genotípico obtenidos a través de estas técnicas en la práctica clínica diaria. Métodos: Trescientas sesenta muestras de piel fueron revisadas retrospectivamente de 149 pacientes diagnosticados según la clasificación WHO-EORTC como: 114 linfomas cutáneos de células T (LCCT) y 35 linfomas cutáneos de células B (LCCB). Doscientas cuarenta y nueve biopsias de 180 pacientes con infiltrados linfoides cutáneos benignos sirvieron de controles. De todos los casos se estudió tejido fijado en formol e incluido en parafina, también se analizaron muestras de sangre periférica de 179 pacientes. Se evaluaron los reordenamientos génicos del receptor de la célula T y de la inmunoglobulina mediante los protocolos de PCR BIOMED-2. La mediana del seguimiento fue de 75,7 y de 45,9 meses en los sujetos con LC y control, respectivamente. Resultados: El protocolo de PCR BIOMED-2 es un método útil para distinguir LCCT de infiltrados T cutáneos benignos con alta sensibilidad (89,4%) y significativa especificidad (81,5%). También proporciona datos valiosos en el diagnóstico particularmente difícil de la micosis fungoide (MF) en estadio inicial que puede imitar dermatosis inflamatorias comunes (sensibilidad = 89,1% y especificidad = 85,5%). El análisis de las recombinaciones de IGH (VH-JH) también ha sido útil para diferenciar LCCB de infiltrados B cutáneos benignos con elevada sensibilidad (85,7%) y especificidad razonable (82,4%). La adición de IGK a la evaluación de IGH aumentó la tasa de detección de clonalidad del 85,7% al 100%, a pesar de, disminuir la especificidad. Se identificó heterogeneidad clonal entre biopsias secuenciales o de diferentes localizaciones en el 14,3% de los LCCT y el 11,8% de los LCCB. La detección de un clon T idéntico en la piel y en la sangre periférica se asocia con peor supervivencia global y específica de la enfermedad en los pacientes con LC primarios, LCCT y MF/síndrome de Sézary. Conclusiones: El protocolo de PCR BIOMED-2 ha demostrado ser una estrategia de diagnóstico útil combinado con los hallazgos clínicos, histológicos e inmunofenotípicos, con algunas implicaciones pronósticas, para estudiar pacientes con proliferaciones linfoides cutáneas. Introduction and Objectives: The standardized BIOMED-2 polymerase chain reaction (PCR) protocols are widely used for detection of clonal populations of T/B-cells and represent an important diagnostic tool in the evaluation of cutaneous lymphomas (CL). The aim of this study was to assess the diagnostic and prognostic value of the genotyping results obtained by these techniques in daily clinical practice. Methods: Three hundred sixty skin samples were retrospectively reviewed from 149 patients diagnosed according to the WHO-EORTC classification as: 114 cutaneous T-cell lymphomas (CTCL) and 35 cutaneous B-cell lymphomas (CBCL). Two hundred forty-nine biopsies from 180 patients with benign cutaneous lymphoid infiltrates served as controls. From all cases formalin-fixed, paraffin-embedded tissue was studied and in 179 patients peripheral blood samples were also analyzed. T-cell receptor and immunoglobulin gene rearrangements were assessed using BIOMED-2 PCR protocols. Median follow-up was 75.7 and 45.9 months in CL and control subjects, respectively. Results: The BIOMED-2 PCR protocol is a useful method in order to distinguish CTCL from benign skin T-cell infiltrates with high sensitivity (89.4%) and meaningful specificity (81.5%). Valuable data is also provided in particularly challenging diagnosis of early-stage mycosis fungoides (MF) that may mimic common inflammatory dermatoses (sensitivity = 89.1% and specificity = 85.5%). Analysis of IGH (VH-JH) rearrangements have also been helpful in differentiating CBCL from benign cutaneous B-cell infiltrates with high sensitivity (85.7%) and reasonable specificity (82.4%). The addition of IGK to IGH assessment increased the clonality detection rate from 85.7% to 100% although decreased specificity. Clonal heterogeneity among sequential or different skin sites biopsies was identified in 14.3% of CTCL and 11.8% of CBCL. Detection of an identical T-cell clone in skin and peripheral blood is associated with worse overall and disease-specific survival rates in primary CL, CTCL and MF/Sézary syndrome patients. Conclusions: The BIOMED-2 PCR protocol has proved to be a useful diagnostic strategy combined with clinical, histologic and immunophenotypic findings, with some prognostic implications, for studying patients with skin lymphoid proliferations. Universitat Autònoma de Barcelona. Programa de Doctorat en Medicina
- Published
- 2021
21. Somatic genomic alterations in lung adenocarcinoma : non-invasive molecular diagnosis and prognosis impact of driver mutations in non-tumoral airway cells
- Author
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Chalela Rengifo, Roberto José, 1985, Gea Guiral, Joaquim, Bellosillo Paricio, Beatriz, Curull Serrano, Víctor, and Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut
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Cáncer de pulmón ,EGFR ,Driver mutations ,KRAS ,Pronóstico ,Mutaciones ,616.2 ,Oncogenes ,Lung cancer ,Adenocarcinoma ,Prognosis - Abstract
La hipótesis general de esta tesis consiste en que durante el proceso de cancerificación del epitelio pulmonar, las “driver-mutations” pueden aparecer no solamente en las células malignas sino también en cualquier célula del epitelio pulmonar sin producir necesariamente expansión clonal. Igualmente hemos querido demostrar que la utilización de muestras citológicas obtenidas mediante cepillado bronquial es válida para el estudio molecular en pacientes con adenocarcinoma pulmonar. Esta tesis se compone de 5 artículos, dos cohortes prospectivas de pacientes con adenocarcinoma intervenido donde pudimos demostrar la presencia de mutaciones en tejido sano y su asociación con mal pronóstico. Un tercer artículo donde demostramos que las muestras citológicas preservadas en RPMI son suficientes para realizar un estudio molecular ampliado. Los dos últimos artículos son una revisión exhaustiva de la etiopatogenia del adenocarcinoma y una editorial de como fenotipos inmunológicos afectan la respuesta a la inmunoterapia en pacientes con cáncer y EPOC. The main hypothesis of this thesis is that during the process of cancerification of the pulmonary epithelium, "driver-mutations" can appear not only in malignant cells but also in any cell of the pulmonary epithelium without necessarily producing clonal expansion. We also wanted to demonstrate that the use of cytological samples obtained by bronchial brushing is valid for the molecular study in patients with pulmonary adenocarcinoma. This thesis consists of 5 articles, two prospective cohorts of patients with resected adenocarcinoma where we could demonstrate the presence of oncogenes mutations in healthy tissue and its association with poor prognosis. A third article where we demonstrated that the cytological samples preserved in RPMI medium are sufficient to perform an extended molecular study. The last two articles are a comprehensive review of the etiopathogenesis of adenocarcinoma and an editorial on how immunological phenotypes affect the response to immunotherapy in patients with cancer and COPD.
- Published
- 2018
22. Estudio de marcadores moleculares en neoplasias mieloproliferativas
- Author
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Martínez Avilés, Luz María, Agència de Gestió d'Ajuts Universitaris i de Recerca, and Bellosillo Paricio, Beatriz
- Subjects
Trastorns mieloproliferatius -- Aspectes genètics - Abstract
Las neoplasias mieloproliferativas (NM) son un grupo de enfermedades clonales de la célula hematopoyética madre. Entre las NM clásicas se encuentran la policitemia vera (PV), la trombocitemia esencial (TE) y la mielofibrosis primaria (MFP). Durante muchos años el diagnóstico de estas patologías se hacía por exclusión utilizando biomarcadores de clonalidad poco específicos. En el año 2005, la descripción de la mutación JAK2V617F supuso un avance importante en el diagnóstico de estas patologías. Posteriormente, se han descrito mutaciones en otros genes como mutaciones en MPL, TET2, ASXL1, IDH1, IDH2, c-CBL, EZH2, IKZF1 y LNK, en distintas neoplasias mieloides y en porcentaje variable. Aun así, ninguno de estos genes son marcadores específicos de ninguna NM y todavía existe un porcentaje elevado de pacientes con TE y MFP sin un marcador de clonalidad conocido. Además, todos estos genes se han descrito como eventos genéticos implicados en la transformación de una NM a leucemia mieloide aguda. El objetivo de este proyecto fue estudiar varios marcadores moleculares en neoplasias mieloproliferativas Philadelphia negativas. En primer lugar, se estudió la modulación de la carga alélica JAK2V617F en pacientes con PV o TE que recibieron tratamiento citoreductor y a su vez se analizó la dinámica natural de la carga alélica en pacientes que no recibieron tratamiento. Posteriormente, se analizaron la presencia de alteraciones en los genes previamente mencionados, en distintos grupos de pacientes. En primer lugar, se analizó la presencia de mutaciones en TET2, ASXL1, IDH1, IDH2 y CBL en un grupo de pacientes JAK2 y MPL negativos, para determinar la frecuencia de alteraciones de estos genes en este grupo de pacientes y determinar su valor en el diagnóstico de estas patologías. En segundo lugar, se estudió la presencia de mutaciones en estos genes incluyendo EZH2, IKZF1 y LNK para estudiar la incidencia y el valor pronóstico de estas alteraciones en las NM que progresan a mielofibrosis. Myeloproliferative neoplasms are a group of clonal disorders of the hematopoietic progenitors. The classical MPN include the polycythemia vera (PV), the essential thrombocythemia and the primary myelofibrosis (PMF). For many years the diagnosis of a MPN was done by exclusion using different biomarkers of clonality. In 2005, the description of the JAK2V617F was a major step in the diagnosis of these malignancies. Afterwards, mutations in other genes as MPL, TET2, ASXL1, IDH1, IDH2, c-CBL, EZH2, IKZF1 and LNK have been described in different myeloid malignancies in variable frequency. Nevertheless alterations in these genes are not disease specific and still remains a high percentage of ET and PMF patients without a molecular marker of clonality. In addition, alteration in these genes have also been described as genetic events involved in the progression of a MPN to acute myeloid leukemia. The aim of this project was the study several molecular markers in myeloproliferative neoplasms Philadelphia negative. Firstly, we analyzed the modulation of the JAK2V617F allele burden in PV and ET patients who received cytoreductive therapy with hydroxicarbamide and we also analysed the natural evolution of the JAK2V617F allele burden in patients who did not received any cytoreductive therapy. We performed two additional projects where we analyzed the presence of mutations in the aforementioned genes in two different cohorts of patients. Firstly we analyzed mutations in TET2, ASXL1, IDH1, IDH2 and CBL in patients JAK2 and MPL negative, to determine the frequency of mutations in these genes and their role in the diagnosis of these malignancies. Secondly, we to study the frequency of mutation in these genes, but also in EZH2, IKZF1 and LNK in PV and ET patients who underwent myelofibrotic transformation to study the incidence of mutations in these genes and their role in the myelofibrotic transformation of a MPN.
- Published
- 2012
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