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1. STATegra, a comprehensive multi-omics dataset of B-cell differentiation in mouse.

Author

Gomez-Cabrero, David, Tarazona, Sonia, Ferreirós-Vidal, Isabel, Ramirez, Ricardo, Company, Carlos, Schmidt, Andreas, Reijmers, Theo, Paul, Veronica, Marabita, Francesco, Rodríguez-Ubreva, Javier, Garcia-Gomez, Antonio, Carroll, Thomas, Cooper, Lee, Liang, Ziwei, Dharmalingam, Gopuraja, van der Kloet, Frans, Harms, Amy, Balzano-Nogueira, Leandro, Lagani, Vincenzo, Tsamardinos, Ioannis, Lappe, Michael, Maier, Dieter, Westerhuis, Johan, Hankemeier, Thomas, Imhof, Axel, Ballestar, Esteban, Mortazavi, Ali, Merkenschlager, Matthias, Tegner, Jesper, and Conesa, Ana

Subjects
Animals, B-Lymphocytes, Cell Differentiation, Cell Line, Genomics, Metabolomics, Mice, Proteomics
Abstract

Multi-omics approaches use a diversity of high-throughput technologies to profile the different molecular layers of living cells. Ideally, the integration of this information should result in comprehensive systems models of cellular physiology and regulation. However, most multi-omics projects still include a limited number of molecular assays and there have been very few multi-omic studies that evaluate dynamic processes such as cellular growth, development and adaptation. Hence, we lack formal analysis methods and comprehensive multi-omics datasets that can be leveraged to develop true multi-layered models for dynamic cellular systems. Here we present the STATegra multi-omics dataset that combines measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. STATegra includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and it is complemented with single-cell data. To our knowledge, the STATegra collection is the most diverse multi-omics dataset describing a dynamic biological system.

Published
2019

4. Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease

Author

Garcia-Gomez, Antonio, Li, Tianlu, de la Calle-Fabregat, Carlos, Rodríguez-Ubreva, Javier, Ciudad, Laura, Català-Moll, Francesc, Godoy-Tena, Gerard, Martín-Sánchez, Montserrat, San-Segundo, Laura, Muntión, Sandra, Morales, Xabier, Ortiz-de-Solórzano, Carlos, Oyarzabal, Julen, San José-Enériz, Edurne, Esteller, Manel, Agirre, Xabier, Prosper, Felipe, Garayoa, Mercedes, and Ballestar, Esteban

Published
2021
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11. The Chromatin Remodeling Complex Chd4/NuRD Controls Striated Muscle Identity and Metabolic Homeostasis

Author

Gómez-del Arco, Pablo, Perdiguero, Eusebio, Yunes-Leites, Paula Sofia, Acín-Pérez, Rebeca, Zeini, Miriam, Garcia-Gomez, Antonio, Sreenivasan, Krishnamoorthy, Jiménez-Alcázar, Miguel, Segalés, Jessica, López-Maderuelo, Dolores, Ornés, Beatriz, Jiménez-Borreguero, Luis Jesús, D’Amato, Gaetano, Enshell-Seijffers, David, Morgan, Bruce, Georgopoulos, Katia, Islam, Abul B.M.M.K., Braun, Thomas, de la Pompa, José Luis, Kim, Johnny, Enriquez, José A., Ballestar, Esteban, Muñoz-Cánoves, Pura, and Redondo, Juan Miguel

Published
2016
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12. Inflammatory cytokines and organ dysfunction associate with the aberrant DNA methylome of monocytes in sepsis

Author

Lorente-Sorolla, Clara, Garcia-Gomez, Antonio, Català-Moll, Francesc, Toledano, Víctor, Ciudad, Laura, Avendaño-Ortiz, José, Maroun-Eid, Charbel, Martín-Quirós, Alejandro, Martínez-Gallo, Mónica, Ruiz-Sanmartín, Adolfo, del Campo, Álvaro García, Ferrer-Roca, Ricard, Ruiz-Rodriguez, Juan Carlos, Álvarez-Errico, Damiana, López-Collazo, Eduardo, and Ballestar, Esteban

Published
2019
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13. Supplementary Figures from The Novel Pan-PIM Kinase Inhibitor, PIM447, Displays Dual Antimyeloma and Bone-Protective Effects, and Potently Synergizes with Current Standards of Care

Author

Paíno, Teresa, primary, Garcia-Gomez, Antonio, primary, González-Méndez, Lorena, primary, San-Segundo, Laura, primary, Hernández-García, Susana, primary, López-Iglesias, Ana-Alicia, primary, Algarín, Esperanza M., primary, Martín-Sánchez, Montserrat, primary, Corbacho, David, primary, Ortiz-de-Solorzano, Carlos, primary, Corchete, Luis A., primary, Gutiérrez, Norma C., primary, Maetos, María-Victoria, primary, Garayoa, Mercedes, primary, and Ocio, Enrique M., primary

Published
2023
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14. Supplementary Tables from The Novel Pan-PIM Kinase Inhibitor, PIM447, Displays Dual Antimyeloma and Bone-Protective Effects, and Potently Synergizes with Current Standards of Care

Author

Paíno, Teresa, primary, Garcia-Gomez, Antonio, primary, González-Méndez, Lorena, primary, San-Segundo, Laura, primary, Hernández-García, Susana, primary, López-Iglesias, Ana-Alicia, primary, Algarín, Esperanza M., primary, Martín-Sánchez, Montserrat, primary, Corbacho, David, primary, Ortiz-de-Solorzano, Carlos, primary, Corchete, Luis A., primary, Gutiérrez, Norma C., primary, Maetos, María-Victoria, primary, Garayoa, Mercedes, primary, and Ocio, Enrique M., primary

Published
2023
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16. JAK2-STAT Epigenetically Regulates Tolerized Genes in Monocytes in the First Encounter With Gram-Negative Bacterial Endotoxins in Sepsis

Author

Morante-Palacios, Octavio, primary, Lorente-Sorolla, Clara, additional, Ciudad, Laura, additional, Calafell-Segura, Josep, additional, Garcia-Gomez, Antonio, additional, Català-Moll, Francesc, additional, Ruiz-Sanmartín, Adolfo, additional, Martínez-Gallo, Mónica, additional, Ferrer, Ricard, additional, Ruiz-Rodriguez, Juan Carlos, additional, Álvarez-Errico, Damiana, additional, and Ballestar, Esteban, additional

Published
2021
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19. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author

Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Martinez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugan, Jordi, Carmona-Saez, Pedro, Toro-Dominguez, Daniel, Carnero-Montoro, Elena, Teruel, Maria, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodriguez-Ubreva, Javier, Garcia-Gomez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Maranon, Concepcion, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocio, Garrancho, Francisco Javier, Lopez-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Hector, Almeida, Isabel, Azevedo, Nancy, Brandao, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fatima, Marinho, Antonio, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martinez, Alfonso, Genre, Fernanda, Lopez Mejias, Raquel, Gonzalez-Gay, Miguel A., Remuzgo, Sara, Ubilla Garcia, Begona, Cervera, Ricard, Espinosa, Gerard, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Diaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernandez Roldan, Maria Concepcion, Jimenez Gomez, Yolanda, Jimenez Moleon, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurelie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valerie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouviere, Benedicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, Dufour, Aleksandra, Wynar, Donatienne, Balog, Attila, Bocskai, Marta, Deak, Magdolna, Dulic, Sonja, Kadar, Gabriella, Kovacs, Laszlo, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegard, Johan, Martin, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Alarcon-Riquelme, Marta E., Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Martinez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugan, Jordi, Carmona-Saez, Pedro, Toro-Dominguez, Daniel, Carnero-Montoro, Elena, Teruel, Maria, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodriguez-Ubreva, Javier, Garcia-Gomez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Maranon, Concepcion, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocio, Garrancho, Francisco Javier, Lopez-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Hector, Almeida, Isabel, Azevedo, Nancy, Brandao, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fatima, Marinho, Antonio, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martinez, Alfonso, Genre, Fernanda, Lopez Mejias, Raquel, Gonzalez-Gay, Miguel A., Remuzgo, Sara, Ubilla Garcia, Begona, Cervera, Ricard, Espinosa, Gerard, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Diaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernandez Roldan, Maria Concepcion, Jimenez Gomez, Yolanda, Jimenez Moleon, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurelie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valerie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouviere, Benedicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, Dufour, Aleksandra, Wynar, Donatienne, Balog, Attila, Bocskai, Marta, Deak, Magdolna, Dulic, Sonja, Kadar, Gabriella, Kovacs, Laszlo, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegard, Johan, Martin, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, and Alarcon-Riquelme, Marta E.

Abstract

Objective Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. Methods Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. Results Four clusters were identified and validated. Three were pathologic, representing inflammatory, lymphoid, and interferon patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. Conclusion Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.

Published
2021

20. MOESM3 of Inflammatory cytokines and organ dysfunction associate with the aberrant DNA methylome of monocytes in sepsis

Author

Lorente-Sorolla, Clara, Garcia-Gomez, Antonio, Català-Moll, Francesc, Toledano, Víctor, Ciudad, Laura, Avendaño-Ortiz, José, Maroun-Eid, Charbel, Martín-Quirós, Alejandro, Martínez-Gallo, Mónica, Ruiz-Sanmartín, Adolfo, Campo, Álvaro, Ferrer-Roca, Ricard, Ruiz-Rodriguez, Juan, Álvarez-Errico, Damiana, López-Collazo, Eduardo, and Ballestar, Esteban

Abstract

Additional file 3: Figure S1. Purification and quality of monocytes. (a) Flow cytometry profiles indicating the sorting strategy and gates used in the study. (b) Cell type deconvolution of the hybridized samples using Houseman algorithm.

Published
2019
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21. Inflammatory cytokines and organ dysfunction associate with the aberrant DNA methylome of monocytes in sepsis

Author

Lorente-Sorolla, C., Garcia-Gomez, Antonio, Català-Moll, Francesc, Toledano, Víctor, Ciudad, Laura, Avendaño-Ortiz, José, Maroun-Eid, Charbel, Martín-Quirós, Alejandro, Martínez-Gallo, Mónica, Ruiz-Sanmartín, Adolfo, del Campo, Álvaro García, Ferrer, Ricard, Ruiz-Rodriguez, Juan Carlos, Álvarez-Errico, Damiana, Ballestar, Esteban, VHIR Vall d'Hebron Institut de Recerca, and Universitat Autònoma de Barcelona

Subjects
DNA methylation, Sepsis, Cytokines, Endotoxin tolerance, Monocytes
Abstract

Sepsis, a life-threatening organ dysfunction caused by a dysregulated systemic immune response to infection, associates with reduced responsiveness to subsequent infections. How such tolerance is acquired is not well understood but is known to involve epigenetic and transcriptional dysregulation. Bead arrays were used to compare global DNA methylation changes in patients with sepsis, non-infectious systemic inflammatory response syndrome, and healthy controls. Bioinformatic analyses were performed to dissect functional reprogramming and signaling pathways related to the acquisition of these specific DNA methylation alterations. Finally, in vitro experiments using human monocytes were performed to test the induction of similar DNA methylation reprogramming. Here, we focused on DNA methylation changes associated with sepsis, given their potential role in stabilizing altered phenotypes. Tolerized monocytes from patients with sepsis display changes in their DNA methylomes with respect to those from healthy controls, affecting critical monocyte-related genes. DNA methylation profiles correlate with IL-10 and IL-6 levels, significantly increased in monocytes in sepsis, as well as with the Sequential Organ Failure Assessment score; the observed changes associate with TFs and pathways downstream to toll-like receptors and inflammatory cytokines. In fact, in vitro stimulation of toll-like receptors in monocytes results in similar gains and losses of methylation together with the acquisition of tolerance. We have identified a DNA methylation signature associated with sepsis that is downstream to the response of monocytes to inflammatory signals associated with the acquisition of a tolerized phenotype and organic dysfunction.

Published
2019

22. SIRT1/2 orchestrate acquisition of DNA methylation and loss of histone H3 activating marks to prevent premature activation of inflammatory genes in macrophages

Author

Li, Tianlu, primary, Garcia-Gomez, Antonio, additional, Morante-Palacios, Octavio, additional, Ciudad, Laura, additional, Özkaramehmet, Sevgi, additional, Van Dijck, Evelien, additional, Rodríguez-Ubreva, Javier, additional, Vaquero, Alejandro, additional, and Ballestar, Esteban, additional

Published
2019
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23. Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease

Author

Garcia-Gomez, Antonio, primary, Li, Tianlu, additional, Rodríguez-Ubreva, Javier, additional, Ciudad, Laura, additional, Català-Moll, Francesc, additional, Martín-Sánchez, Montserrat, additional, San-Segundo, Laura, additional, Morales, Xabier, additional, Ortiz de Solórzano, Carlos, additional, Oyarzabal, Julen, additional, San José-Enériz, Edurne, additional, Agirre, Xabier, additional, Prosper, Felipe, additional, Garayoa, Mercedes, additional, and Ballestar, Esteban, additional

Published
2019
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24. Inflammatory cytokines shape a changing DNA methylome in monocytes mirroring disease activity in rheumatoid arthritis

Author

Rodríguez-Ubreva, Javier, primary, de la Calle-Fabregat, Carlos, additional, Li, Tianlu, additional, Ciudad, Laura, additional, Ballestar, Maria L, additional, Català-Moll, Francesc, additional, Morante-Palacios, Octavio, additional, Garcia-Gomez, Antonio, additional, Celis, Raquel, additional, Humby, Frances, additional, Nerviani, Alessandra, additional, Martin, Javier, additional, Pitzalis, Costantino, additional, Cañete, Juan D, additional, and Ballestar, Esteban, additional

Published
2019
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25. STATegra: a comprehensive multi-omics dataset of B-cell differentiation in mouse

Author

Gomez-Cabrero, David, primary, Tarazona, Sonia, additional, Ferreirós-Vidal, Isabel, additional, Ramirez, Ricardo N., additional, Company, Carlos, additional, Schmidt, Andreas, additional, Reijmers, Theo, additional, Saint Paul, Veronica von, additional, Marabita, Francesco, additional, Rodríguez-Ubreva, Javier, additional, Garcia-Gomez, Antonio, additional, Carroll, Thomas, additional, Cooper, Lee, additional, Liang, Ziwei, additional, Dharmalingam, Gopuraja, additional, van der Kloet, Frans, additional, Harms, Amy C., additional, Balzano-Nogueira, Leandro, additional, Lagani, Vicenzo, additional, Tsamardinos, Ioannis, additional, Lappe, Michael, additional, Maier, Dieter, additional, Westerhuis, Johan A., additional, Hankemeier, Thomas, additional, Imhof, Axel, additional, Ballestar, Esteban, additional, Mortazavi, Ali, additional, Merkenschlager, Matthias, additional, Tegner, Jesper, additional, and Conesa, Ana, additional

Published
2019
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26. Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites

Author

Rodríguez-Cortez, Virginia C., primary, Martínez-Redondo, Paloma, additional, Català-Moll, Francesc, additional, Rodríguez-Ubreva, Javier, additional, Garcia-Gomez, Antonio, additional, Poorani-Subramani, Ganesh, additional, Ciudad, Laura, additional, Hernando, Henar, additional, Pérez-García, Arantxa, additional, Company, Carlos, additional, Urquiza, José M., additional, Ramiro, Almudena R., additional, Di Noia, Javier M., additional, Vaquero, Alejandro, additional, and Ballestar, Esteban, additional

Published
2017
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27. TET2- and TDG-mediated changes are required for the acquisition of distinct histone modifications in divergent terminal differentiation of myeloid cells

Author

Garcia-Gomez, Antonio, primary, Li, Tianlu, additional, Kerick, Martin, additional, Català-Moll, Francesc, additional, Comet, Natalia R., additional, Rodríguez-Ubreva, Javier, additional, de la Rica, Lorenzo, additional, Branco, Miguel R., additional, Martín, Javier, additional, and Ballestar, Esteban, additional

Published
2017
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29. The Novel Pan-PIM Kinase Inhibitor, PIM447, Displays Dual Antimyeloma and Bone-Protective Effects, and Potently Synergizes with Current Standards of Care

Author

Paíno, Teresa, primary, Garcia-Gomez, Antonio, additional, González-Méndez, Lorena, additional, San-Segundo, Laura, additional, Hernández-García, Susana, additional, López-Iglesias, Ana-Alicia, additional, Algarín, Esperanza M., additional, Martín-Sánchez, Montserrat, additional, Corbacho, David, additional, Ortiz-de-Solorzano, Carlos, additional, Corchete, Luis A., additional, Gutiérrez, Norma C., additional, Maetos, María-Victoria, additional, Garayoa, Mercedes, additional, and Ocio, Enrique M., additional

Published
2017
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30. Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

Author

Garcia-Gomez, Antonio, primary, Las Rivas, Javier De, additional, Ocio, Enrique M., additional, Díaz-Rodríguez, Elena, additional, Montero, Juan C., additional, Martín, Montserrat, additional, Blanco, Juan F., additional, Sanchez-Guijo, Fermín M., additional, Pandiella, Atanasio, additional, San Miguel, Jesús F., additional, and Garayoa, Mercedes, additional

Published
2014
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31. Preclinical Activity of the Oral Proteasome Inhibitor MLN9708 in Myeloma Bone Disease

Author

Garcia-Gomez, Antonio, primary, Quwaider, Dalia, additional, Canavese, Miriam, additional, Ocio, Enrique M., additional, Tian, Ze, additional, Blanco, Juan F., additional, Berger, Allison J., additional, Ortiz-de-Solorzano, Carlos, additional, Hernández-Iglesias, Teresa, additional, Martens, Anton C.M., additional, Groen, Richard W.J., additional, Mateo-Urdiales, Joaquín, additional, Fraile, Susana, additional, Galarraga, Miguel, additional, Chauhan, Dharminder, additional, San Miguel, Jesús F., additional, Raje, Noopur, additional, and Garayoa, Mercedes, additional

Published
2014
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36. Dasatinib as a Bone-Modifying Agent: Anabolic and Anti-Resorptive Effects

Author

Garcia-Gomez, Antonio, primary, Ocio, Enrique M., additional, Crusoe, Edvan, additional, Santamaria, Carlos, additional, Hernández-Campo, Pilar, additional, Blanco, Juan F., additional, Sanchez-Guijo, Fermin M., additional, Hernández-Iglesias, Teresa, additional, Briñón, Jesús G., additional, Fisac-Herrero, Rosa M., additional, Lee, Francis Y., additional, Pandiella, Atanasio, additional, San Miguel, Jesús F., additional, and Garayoa, Mercedes, additional

Published
2012
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37. Epoxyketone-Based Proteasome Inhibitors Carfilzomib and Orally Bioavailable ONX 0912 Have Anti-Resorptive and Bone-Anabolic Activity in Addition to Anti-Myeloma Effects

Author

Hurchla, Michelle A, primary, Garcia-Gomez, Antonio, additional, Hornick, Mary C, additional, Ocio, Enrique M, additional, Li, Aixiao, additional, Blanco, Juan F, additional, Collins, Lynne, additional, Kirk, Christopher J, additional, Piwnica-Worms, David, additional, Vij, Ravi, additional, Tomasson, Michael H, additional, Pandiella, Atanasio, additional, San Miguel, Jesús F, additional, Garayoa, Mercedes, additional, and Weilbaecher, Katherine N, additional

Published
2011
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38. Reversibility of the Resistance to Lenalidomide and Pomalidomide and Absence of Cross-Resistance in a Murine Model of MM

Author

Ocio, Enrique M, primary, Fernández-Lázaro, Diego, additional, San-Segundo, Laura, additional, González-Méndez, Lorena, additional, Martín-Sánchez, Montserrat, additional, Garayoa, Mercedes, additional, Paíno, Teresa, additional, Garcia-Gomez, Antonio, additional, Gutierrez, Norma C., additional, Delgado, Manuel, additional, Montero, Juan C., additional, Quintana, Nuria, additional, García, Jose Luis, additional, Pandiella, Atanasio, additional, and San Miguel, Jesús F., additional

Published
2011
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39. Transcriptomic rationale for the synergy observed with dasatinib + bortezomib + dexamethasone in multiple myeloma

Author

de Queiroz Crusoe, Edvan, primary, Maiso, Patricia, additional, Fernandez-Lazaro, Diego, additional, San-Segundo, Laura, additional, Garayoa, Mercedes, additional, Garcia-Gomez, Antonio, additional, Gutierrez, Norma C., additional, Delgado, Manuel, additional, Colado, Enrique, additional, Martin-Sanchez, Jesus, additional, Lee, Francis Y., additional, and Ocio, Enrique M., additional

Published
2011
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40. Dasatinib Promotes Osteoprogenitor Differentiation and Inhibition of Osteoclastogenesis: Rationale for Treatment of Myeloma Bone Disease.

Author

Garcia-Gomez, Antonio, primary, Garayoa, Mercedes, additional, Ocio, Enrique M., additional, Crusoe, Edvan, additional, Fernández, Diego, additional, Paíno, Teresa, additional, Segundo, Laura San, additional, Montero, Juan C., additional, Álvarez-Fernández, Stela, additional, Blanco, Juan F., additional, Sanchez-Guijo, Fermin M., additional, Garzon, Felix T., additional, Pandiella, Atanasio, additional, and San-Miguel, Jesús F., additional

Published
2009
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41. Transcriptomic rationale for the synergy observed with dasatinib + bortezomib + dexamethasone in multiple myeloma.

Author

Queiroz Crusoe, Edvan, Maiso, Patricia, Fernandez-Lazaro, Diego, San-Segundo, Laura, Garayoa, Mercedes, Garcia-Gomez, Antonio, Gutierrez, Norma, Delgado, Manuel, Colado, Enrique, Martin-Sanchez, Jesus, Lee, Francis, and Ocio, Enrique

Subjects
MULTIPLE myeloma, BONE marrow, PERMUTATIONS, GENE expression, HEREDITY
Abstract

Despite the advantage observed with novel drugs such as bortezomib, thalidomide, or lenalidomide, multiple myeloma (MM) remains incurable and there is a clear need for new drugs or combinations based on the pathogenetic mechanism of MM. One of the proposed mechanisms in MM pathogenesis is the involvement of kinase molecules in the growth and survival of myelomatous cells. In this study, we have explored the optimal combination for dasatinib, a tyrosine kinase inhibitor, in MM cells. A clear synergistic effect was observed with the triple combination of dasatinib with bortezomib and dexamethasone which was evident even in the presence of bone marrow microenvironment. Experiments performed on freshly isolated patients' cells also demonstrated potentiation of response in the triple as compared with the agents alone or in double combinations. Gene expression profiling experiments provided some clues on the transcriptional rationale underlying this potentiation, as the triple combination led to significant deregulation of genes involved in cell death, cell growth, proliferation, DNA replication, repair and recombination, and cell-cell signaling. Some of these results were further confirmed by apoptosis and cell cycle experiments and also by Western blot and PCR. These data provide the rationale for the use of this novel combination in MM patients. [ABSTRACT FROM AUTHOR]

Published
2012
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