Prosper-Cardoso, F. (Felipe)
- Publications
- item.page.relationships.isContributorAdvisorOfPublication
- item.page.relationships.isContributorOfPublication
217 results
Filtering
Settings
Search Results
Now showing 1 - 10 of 217
- Determinación de enfermedad mínima residual molecular en sangre periférica mediante NGS como nueva herramienta en el seguimiento posttrasplante alogénico de progenitores hematopoyéticos(2019) Fernandez-Mercado, M. (Marta); Aguilera-Díaz, A. (Almudena); Arnedo, P. (P.); Bandres, E. (Eva); Viguria, M.C. (María C.); Aguirre-Ruiz, P. (P.); Zudaire, M.T. (Maria Teresa); Redondo, M. (M.); Vazquez, I. (Iria); Larrayoz, M.J. (María J.); Jauregui, A. (A.); Prosper-Cardoso, F. (Felipe); Mateos, M.C. (María C.); Blasco-Iturri, Z. (Zuriñe); Calasanz-Abinzano, M.J. (Maria Jose)La determinación de la EMR en médula ósea y del quimerismo hematopoyético (QH) en sangre periférica (SP), son herramientas imprescindibles para detectar recaídas en el seguimiento post-alo-TPH. La combinación de tecnologías más sensibles, que identifiquen cambios en el QH, y más específicos que detecten recaídas en sangre periférica, pueden complementar los estudios de EMR realizados en médula ósea (MO) y permitir tomar decisiones clínicas más precoces y específicas. El objetivo de este estudio fue valorar la aplicabilidad clínica de determinar la EMR molecular mediante Next Generation Sequencing (NGS) en SP en aquellos momentos en los que se observa un cambio del QH.
- Mutation patterns of 16 genes in primary and secondary acute myeloid leukemia (AML) with normal cytogenetics(2012) Kondo, T. (Toshinori); McDonald, E.J. (Emma Jane); Perez, C. (Cristina); Fernandez-Mercado, M. (Marta); Wainscoat, J.S. (James S.); Pellagatti, A. (Andrea); Davies, C. (Carwyn); Boultwood, J. (Jacqueline); Larrayoz, M.J. (María J.); Prosper-Cardoso, F. (Felipe); Calasanz-Abinzano, M.J. (Maria Jose); Yip, B.H. (Bon Ham); Odero, M.D. (Maria Dolores); Aguirre-Ena, X. (Xabier); Killick, S. (Sally)Abstract Acute myeloid leukemia patients with normal cytogenetics (CN-AML) account for almost half of AML cases. We aimed to study the frequency and relationship of a wide range of genes previously reported as mutated in AML (ASXL1, NPM1, FLT3, TET2, IDH1/2, RUNX1, DNMT3A, NRAS, JAK2, WT1, CBL, SF3B1, TP53, KRAS and MPL) in a series of 84 CN-AML cases. The most frequently mutated genes in primary cases were NPM1 (60.8%) and FLT3 (50.0%), and in secondary cases ASXL1 (48.5%) and TET2 (30.3%). We showed that 85% of CN-AML patients have mutations in at least one of ASXL1, NPM1, FLT3, TET2, IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations; seventeen cases presented mutations of at least one of these genes. However, there was no consistent pattern in mutation acquisition during disease progression. This report concerns the analysis of the largest number of gene mutations in CN-AML studied to date, and provides insight into the mutational profile of CN-AML
- Epigenetic Signatures Associated with Different Levels of Differentiation Potential in Human Stem Cells(Public Library of Science, 2009) Cigudosa, J.C. (Juan Cruz); Roman-Gomez, J. (José); Ballestar, E. (E.); Aranda, P. (P.); Prieto, I. (Inés); Andreu, E.J. (Enrique José); Siebert, R. (Reiner); Esteller, M. (Manel); Prosper-Cardoso, F. (Felipe); Aguirre-Ena, X. (Xabier); Martin-Subero, J.I. (Jose Ignacio)The therapeutic use of multipotent stem cells depends on their differentiation potential, which has been shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic profiles.
- Downregulation of DBC1 expression in acute lymphoblastic leukaemia is mediated by aberrant methylation of its promoter(American Society of Hematology, 2006) Cordeu, L. (Lucía); Jimenez-Velasco, A. (A.); Roman-Gomez, J. (José); San-Jose-Eneriz, E. (Edurne); Heiniger, A. (A.); Garate, L. (Leire); Vazquez, I. (Iria); Prosper-Cardoso, F. (Felipe); Torres, A. (Antonio); Calasanz-Abinzano, M.J. (Maria Jose); Aguirre-Ena, X. (Xabier)The DBC1 gene is a potential tumour suppressor gene that is commonly hypermethylated in epithelial cancers. We studied the role of promoter hypermethylation in the regulation of DBC1 in acute lymphoblastic leukaemia (ALL) cell lines and 170 ALL patients at diagnosis. Abnormal methylation of DBC1 was observed in all ALL cell lines and in 17% of ALL patients. Moreover, DBC1 methylation was associated with decreased DBC1 expression, while treatment of ALL cells with 5-Aza-2¢-deoxycytidine resulted in demethylation of the promoter and upregulation of DBC1 expression. Fluorescence in situ hybridisation identified the deletion of one allele of DBC1 in some ALL cell lines, which indicated that the lack of DBC1 expression was due to deletion of one allele and methylation of the other. In conclusion, these results demonstrate, for the first time, that the expression of DBC1 is downregulated in a percentage of patients with ALL due to the hypermethylation of its promoter and/or gene deletion.
- Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design(2020) Ariceta, B. (Beñat); Fernandez-Mercado, M. (Marta); Aguilera-Díaz, A. (Almudena); Prieto-Conde, M.I. (María Isabel); García-Sanz, R. (Ramón); Palomino-Echeverría, S. (Sara); Mañú, A. (Amagoia); Alfonso-Piérola, A. (Ana); Vazquez, I. (Iria); Larrayoz, M.J. (María J.); Prosper-Cardoso, F. (Felipe); Chillón, M.C. (María del Carmen); Blasco-Iturri, Z. (Zuriñe); Calasanz-Abinzano, M.J. (Maria Jose)The diagnosis of myeloid neoplasms (MN) has significantly evolved through the last few decades. Next Generation Sequencing (NGS) is gradually becoming an essential tool to help clinicians with disease management. To this end, most specialized genetic laboratories have implemented NGS panels targeting a number of different genes relevant to MN. The aim of the present study is to evaluate the performance of four different targeted NGS gene panels based on their technical features and clinical utility. A total of 32 patient bone marrow samples were accrued and sequenced with 3 commercially available panels and 1 custom panel. Variants were classified by two geneticists based on their clinical relevance in MN. There was a difference in panel¿s depth of coverage. We found 11 discordant clinically relevant variants between panels, with a trend to miss long insertions. Our data show that there is a high risk of finding different mutations depending on the panel of choice, due both to the panel design and the data analysis method. Of note, CEBPA, CALR and FLT3 genes, remains challenging the use of NGS for diagnosis of MN in compliance with current guidelines. Therefore, conventional molecular testing might need to be kept in place for the correct diagnosis of MN for now.
- Células madre y cáncer: dilucidando el origen de la célula madre tumoral(Ediciones Universidad de Navarra, 2007) Lopez-Picazo, J.M. (José M.); Garcia-Foncillas, J. (Jesús); Prosper-Cardoso, F. (Felipe); Bosch-Barrera, J. (Joaquim)La terapia con células madre está en la vanguardia de la investigación biomédica actual. Cada vez hay más evidencias de que la célula madre tumoral puede estar implicada en el origen del cáncer como se propone en el modelo jerárquico. La célula madre puede transformarse en maligna por procesos de pérdida de la división asimétrica, transferencia gené- tica horizontal, fusión celular, factores microambientales y los agentes carcinógenos ya descritos para las células diferenciadas. Conocer mejor cómo se produce esta transformación permitirá diseñar abordajes de terapia celular más seguros y nuevos tratamientos específi cos contra estas células madre tumorales. INGLÉS: Stem cell therapy is currently at the frontier of biomedical research. A considerable volume of evidence indicates that cancer stem cells are responsible for the development of different types of tumors. Malignant transformation of stem cells may be due to the loss of normal asymmetric division processes, cell fusion, microenviromental factors, generic and epigenetic mechanisms or carcinogenics already implicated in cancer development. A better understanding of these transforming events will allow more rational design of new specific therapeutic strategies targeting the cancer stem cell.
- LIBRA: an adaptative integrative tool for paired single-cell multi-omics data(2023) Gomez-Cabrero, D. (David); Khan, S.A. (Sumeer A.); Tegner, J. (Jesper); Qu, S. (Sisi); Lehmann, R. (Robert); Martinez-de-Morentin, X. (Xabier); Maillo, A. (Alberto); Kiani, N.A. (Narsis A.); Prosper-Cardoso, F. (Felipe)Background: Single-cell multi-omics technologies allow a profound system-level biology understanding of cells and tissues. However, an integrative and possibly systems-based analysis capturing the different modalities is challenging. In response, bioinformatics and machine learning methodologies are being developed for multi-omics single-cell analysis. It is unclear whether current tools can address the dual aspect of modality integration and prediction across modalities without requiring extensive parameter fine-tuning. Methods: We designed LIBRA, a neural network based framework, to learn translation between paired multi-omics profiles so that a shared latent space is constructed. Additionally, we implemented a variation, aLIBRA, that allows automatic fine-tuning by identifying parameter combinations that optimize both the integrative and predictive tasks. All model parameters and evaluation metrics are made available to users with minimal user iteration. Furthermore, aLIBRA allows experienced users to implement custom configurations. The LIBRA toolbox is freely available as R and Python libraries at GitHub (TranslationalBioinformaticsUnit/LIBRA).Results: LIBRA was evaluated in eight multi-omic single-cell data-sets, including three combinations of omics. We observed that LIBRA is a state-of-the-art tool when evaluating the ability to increase cell-type (clustering) resolution in the integrated latent space. Furthermore, when assessing the predictive power across data modalities, such as predictive chromatin accessibility from gene expression, LIBRA outperforms existing tools. As expected, adaptive parameter optimization (aLIBRA) significantly boosted the performance of learning predictive models from paired data-sets.Conclusion: LIBRA is a versatile tool that performs competitively in both integration and prediction tasks based on single-cell multi-omics data. LIBRA is a data-driven robust platform that includes an adaptive learning scheme.
- Chromosomal abnormalities clustering in multiple myeloma reveals cytogenetic subgroups with nonrandom acquisition of chromosomal changes(Nature Publishing Group, 2004) Cigudosa, J.C. (Juan Cruz); Guillen-Grima, F. (Francisco); Harder, L. (Lana); Siebert, R. (Reiner); Prosper-Cardoso, F. (Felipe); Calasanz-Abinzano, M.J. (Maria Jose); Odero, M.D. (Maria Dolores); Martin-Subero, J.I. (Jose Ignacio); Saez, B. (Borja)
- Pegylated liposomal doxorubicin, melphalan and prednisone therapy for elderly patients with multiple myeloma(Wiley-Blackwell, 2006) Alegre, A. (A.); García-Sanz, R. (Ramón); Hernandez, J.M. (J. M.); Mateos, M.V. (María Victoria); Barez, A. (A.); Garcia-Laraña, J. (J.); Prosper-Cardoso, F. (Felipe); Sureda-Balari, A. M. (Anna Maria); San-Miguel, J.F. (Jesús F.)Melphalan&Prednisone (MP) is considered as the standard therapy for Multiple Myeloma (MM) patients not eligible for high-dose therapy. Here, we report the results of a phase I–II study to evaluate the feasibility and efficacy of the association of PLDto the conventionalMP regimen during the first six cycles of the front-line therapy for untreatedMMpatients older than 70. Thirty patients were included in the study with a median age of 77 years (71–84) and a M/F ratio of 17/13. The phase I of the study demonstrated that the maximum tolerable dose of PLD in this setting was 30mg/m2, so itwas the final dose evaluated in the study. Twenty-nine patients were valuable for response, which was: complete in 4 (14%) partial in 15 (52%) minor/ no changes in 7 (24%) and progressive in 3 (10%). The median progression free survival (PFS) was 24 months. The median overall survival (OS) has not been reached yet, with a 3-year probability for OS and PFS of 52 and 37%, respectively. Haematological toxicity was frequent but usually weak/moderate (grades 1&2 of theWHOscale) and itwas resolved only with dose delays. Infection was a relatively frequent event (30%of patients), but only in 4 cases it was of grade 3. No cases of palmar-plantar erythrodysesthesia were observed. In conclusion, pegylated liposomal doxorubicin can be safely added to the other chemotherapeutic drugs in the treatment of elderly MM patients, which can be very useful for patients in whomnovel agents are not tolerated or inefficient.
- Engineering a Humanised Niche to Support Human Haematopoiesis in Mice: Novel Opportunities in Modelling Cancer(2020) Calvo, I.A. (Isabel A.); Granero-Moltó, F. (Froilán); Flandes-Iparraguirre, M. (María); McGovern, J.A. (Jacqui A.); Landgraf, M. (Marietta); Juan-Pardo, E.M. (Elena M.) de; Nicol, A. (Andrew); Mazo, M. (Manuel); Shafiee, A. (Abbas); Paiva, B. (Bruno); Lahr, C.A. (Christoph A.); Sanchez-Herrero, A. (Alvaro); Prosper-Cardoso, F. (Felipe); Saez, B. (Borja); Bray, L.J. (Laura J.)Despite the bone marrow microenvironment being widely recognised as a key player in cancer research, the current animal models that represent a human haematopoietic system lack the contribution of the humanised marrow microenvironment. Here we describe a murine model that relies on the combination of an orthotopic humanised tissue-engineered bone construct (ohTEBC) with patient-specific bone marrow (BM) cells to create a humanised bone marrow (hBM) niche capable of supporting the engraftment of human haematopoietic cells. Results showed that this model supports the engraftment of human CD34+ cells from a healthy BM with human haematopoietic cells migrating into the mouse BM, human BM compartment, spleen and peripheral blood. We compared these results with the engraftment capacity of human CD34+ cells obtained from patients with multiple myeloma (MM). We demonstrated that CD34+ cells derived from a diseased BM had a reduced engraftment potential compared to healthy patients and that a higher cell dose is required to achieve engraftment of human haematopoietic cells in peripheral blood. Finally, we observed that hematopoietic cells obtained from the mobilised peripheral blood of patients yields a higher number of CD34+, overcoming this problem. In conclusion, this humanised mouse model has potential as a unique and patient-specific pre-clinical platform for the study of tumour–microenvironment interactions, including human bone and haematopoietic cells, and could, in the future, serve as a drug testing platform.