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3. Predictors of outcomes after internal fixation of periprosthetic femoral hip fractures Subgroup analysis of the peri-implant and peri-prosthetic fractures Spanish registry (PIPPAS)

Author

Andrés-Peiró, José Vicente, Nomdedéu, Josep, Aguado, Héctor J, González-Morgado, Diego, Minguell-Monyart, Joan, Joshi-Jubert, Nayana, Teixidor-Serra, Jordi, Tomàs-Hernández, Jordi, Selga-Marsà, Jordi, García-Sánchez, Yaiza, Noriega-González, David C, Mateos-Álvarez, Elvira, Pereda-Manso, Adela, Cervera-Díaz, M Carmen, Balvis-Balvis, Patricia, García-Pérez, Ángela, Rodríguez-Arenas, Mónica, Castro-Menéndez, Manuel, Moreta, Jesús, Olías-López, Beatriz, Amaya-Espinosa, Patricia, Boluda-Mengod, Juan, Bárcena-Goitilandia, Leopoldo, Blas-Dobón, José Antonio, Freile-Pazmiño, Patricio, Castillón, Pablo, Lanuza-Lagunilla, Lucía, Cabria-Fernández, Julián, Valle-Cruz, José, García-Coiradas, Javier, Bonome-Roel, César, Cano-Leira, María de los Ángeles, Benjumea-Carrasco, Antonio, Chico-García, Marcos, Fernández-Juan, Alexis, Saura-Sánchez, Eladio, Sánchez-Gómez, Plácido, Ricón-Recarey, Francisco Javier, García-García, Elena María, Medrano-Morte, Isabel, Cuadrado-Abajo, Francisco, Pérez-Núñez, María I, García-González, Sara, Pozo-Manrique, Pedro Del, García-Navas-García, Francisco Manuel, García-Paredero, Ester, Guijarro-Valtueña, Ainhoa, Navas-Pernía, Inés, Videla-Cés, Miquel, Muñoz-Vives, Josep M, Querolt-Coll, Jordi, Triana-López de Santamaría, Guillermo, Serra-Porta, Teresa, Carrasco-Becerra, M Carmen, Pena-Paz, Silvia, Otero-Naveiro, Víctor, Fernández-Dorado, Fátima, Martínez-Menduiña, Amaia, Galián-Muñoz, Elena, Hernández, José M, Renau-Cerrillo, Marina, Campuzano-Bitterling, Borja, Carreras-Castañer, Anna, Vives-Barquiel, Marian, Camacho-Carrasco, Pilar, Jornet-Gibert, Montsant, Muñoz-Vicente, Adrián, Gámez-Asunción, Carla, Plaza-Salazar, Nuria, Benito-Santamaría, Jennifer, Cuenca-Copete, Alejandro, Alonso-Viana, Laura, Mingo-Robinet, Juan, Briso-Montiano, Ricardo, Barbería-Biurrun, Amaya, Chouza-Montero, Laura, Ojeda-Thies, Cristina, Ajuria-Fernández, Eliam, Díaz-Suárez, Rebeca, Gasset-Teixidor, Alfons, Domínguez-Ibarrola, Andrea, Gosálbez, Javier, Pérez-Hevia, Imanol, Riera-Álvarez, Luís, Roche-Albero, Adrián, Macho-Mier, María, Criado-Albillos, Guillermo, Cabello-Benavides, Hugo Gabriel, Cunchillos-Pascual, Jorge, Saló-Cuenca, José Carlos, Espona-Roselló, Jordi, Salamanca-Ontiveros, César, García-Portabella, Pablo, Martínez-Íñiguez Blasco, Jorge, Sevilla-Ortega, Paloma, Cano-Porras, Juan Ramón, Martínez-Díaz, Santos, Carabelli, Guido Sebastián, Slullitel, Pablo, Astore, Ignacio, Hernández-Pascual, Carlos, Marín-Sánchez, Javier, Córdova-Peralta, Julio C, Sánchez-Hernández, Natalia, García-García, Guillermo, Rodríguez-Gangoso, Alfredo, Pérez-Sánchez, José María, Piñeiro-Borrero, Ana, Mandía-Martínez, Alfonso, De Caso-Rodríguez, Julio, Benito-Mateo, Miguel, Murillo-Vizuete, Antonio D, Herrán-Núnez, Gaspar De La, Nunes-Ugarte, Nahikari, Pérez-Salazar, Nicolás Elizalde, De Sande-Díaz, María, García-Fuentes, Xoan D, de Cortázar-Antolín, Unai García, and Sánchez, Daniel Escobar

Published
2024
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4. European LeukemiaNet 2017 risk stratification for acute myeloid leukemia: validation in a risk-adapted protocol

Author

Bataller, Alex, Garrido, Ana, Guijarro, Francesca, Oñate, Guadalupe, Diaz-Beyá, Marina, Arnan, Montserrat, Tormo, Mar, Vives, Susana, de Llano, María Paz Queipo, Coll, Rosa, Gallardo, David, Vall-Llovera, Ferran, Escoda, Lourdes, Garcia-Guiñon, Antonio, Salamero, Olga, Sampol, Antònia, Merchan, Brayan M., Bargay, Joan, Castaño-Díez, Sandra, Esteban, Daniel, Oliver-Caldés, Aina, Rivero, Andrea, Mozas, Pablo, López-Guerra, Mònica, Pratcorona, Marta, Zamora, Lurdes, Costa, Dolors, Rozman, Maria, Nomdedéu, Josep F., Colomer, Dolors, Brunet, Salut, Sierra, Jorge, and Esteve, Jordi

Published
2022
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6. Engraftment characterization of risk-stratified AML in NSGS mice

Author

Díaz de la Guardia, Rafael, Velasco-Hernandez, Talía, Gutiérrez-Agüera, Francisco, Roca-Ho, Heleia, Molina, Oscar, Nombela-Arrieta, Cesar, Bataller, Alex, Fuster, Jose Luis, Anguita, Eduardo, Vives, Susana, Zamora, Lurdes, Nomdedeu, Josep, Gómez-Casares, María Teresa, Ramírez-Orellana, Manuel, Lapillonne, Helene, Ramos-Mejia, Verónica, Rodríguez-Manzaneque, Juan Carlos, Bueno, Clara, Lopez-Millan, Belen, and Menéndez, Pablo

Published
2021
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7. Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial

Author

Voso, Maria Teresa, Larson, Richard A., Jones, Dan, Marcucci, Guido, Prior, Thomas, Krauter, Jürgen, Heuser, Michael, Lavorgna, Serena, Nomdedeu, Josep, Geyer, Susan M., Walker, Alison, Wei, Andrew H., Sierra, Jorge, Sanz, Miguel A., Brandwein, Joseph M., de Witte, Theo M., Jansen, Joop H., Niederwieser, Dietger, Appelbaum, Frederick R., Medeiros, Bruno C., Tallman, Martin S., Schlenk, Richard F., Ganser, Arnold, Amadori, Sergio, Cheng, Yuan, Chen, YinMiao, Pallaud, Celine, Du, Ling, Piciocchi, Alfonso, Ehninger, Gerhard, Byrd, John, Thiede, Christian, Döhner, Konstanze, Stone, Richard M., Döhner, Hartmut, Bloomfield, Clara D., and Lo-Coco, Francesco

Published
2020
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8. Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia

Author

Döhner, Konstanze, Thiede, Christian, Jahn, Nikolaus, Panina, Ekaterina, Gambietz, Agnes, Larson, Richard A., Prior, Thomas W., Marcucci, Guido, Jones, Dan, Krauter, Jürgen, Heuser, Michael, Voso, Maria Teresa, Ottone, Tiziana, Nomdedeu, Josep F., Mandrekar, Sumithra J., Klisovic, Rebecca B., Wei, Andrew H., Sierra, Jorge, Sanz, Miguel A., Brandwein, Joseph M., de Witte, Theo, Jansen, Joop H., Niederwieser, Dietger, Appelbaum, Frederick R., Medeiros, Bruno C., Tallman, Martin S., Schlenk, Richard F., Ganser, Arnold, Serve, Hubert, Ehninger, Gerhard, Amadori, Sergio, Gathmann, Insa, Benner, Axel, Pallaud, Celine, Stone, Richard M., Döhner, Hartmut, and Bloomfield, Clara D.

Published
2020
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11. Detailed Characterization of Mesenchymal Stem/Stromal Cells from a Large Cohort of AML Patients Demonstrates a Definitive Link to Treatment Outcomes

Author

Diaz de la Guardia, Rafael, Lopez-Millan, Belen, Lavoie, Jessie R., Bueno, Clara, Castaño, Julio, Gómez-Casares, Maite, Vives, Susana, Palomo, Laura, Juan, Manel, Delgado, Julio, Blanco, Maria L., Nomdedeu, Josep, Chaparro, Alberto, Fuster, Jose Luis, Anguita, Eduardo, Rosu-Myles, Michael, and Menéndez, Pablo

Published
2017
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12. Validation of the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes in chronic myelomonocytic leukaemia: A novel approach for improved risk stratification.

Author

Mosquera Orgueira, Adrian, Perez Encinas, Manuel Mateo, Diaz Varela, Nicolas, Wang, Yu‐Hung, Mora, Elvira, Diaz‐Beya, Marina, Montoro, Maria Julia, Pomares Marin, Helena, Ramos Ortega, Fernando, Tormo, Mar, Jerez, Andres, Nomdedeu, Josep, de Miguel Sanchez, Carlos, Arenillas, Leonor, Carcel, Paula, Cedena Romero, Maria Teresa, Xicoy Cirici, Blanca, Rivero Arango, Eugenia, Del Orbe Barreto, Rafael Andrés, and Benlloch, Luis

Subjects
MYELODYSPLASTIC syndromes, ARTIFICIAL intelligence, CHRONIC leukemia, OVERALL survival, MYELOID cells, MEDICAL personnel
Abstract

Summary: Chronic myelomonocytic leukaemia (CMML) is a rare haematological disorder characterized by monocytosis and dysplastic changes in myeloid cell lineages. Accurate risk stratification is essential for guiding treatment decisions and assessing prognosis. This study aimed to validate the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes (AIPSS‐MDS) in CMML and to assess its performance compared with traditional scores using data from a Spanish registry (n = 1343) and a Taiwanese hospital (n = 75). In the Spanish cohort, the AIPSS‐MDS accurately predicted overall survival (OS) and leukaemia‐free survival (LFS), outperforming the Revised‐IPSS score. Similarly, in the Taiwanese cohort, the AIPSS‐MDS demonstrated accurate predictions for OS and LFS, showing superiority over the IPSS score and performing better than the CPSS and molecular CPSS scores in differentiating patient outcomes. The consistent performance of the AIPSS‐MDS across both cohorts highlights its generalizability. Its adoption as a valuable tool for personalized treatment decision‐making in CMML enables clinicians to identify high‐risk patients who may benefit from different therapeutic interventions. Future studies should explore the integration of genetic information into the AIPSS‐MDS to further refine risk stratification in CMML and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Development and validation of a comprehensive genomic diagnostic tool for myeloid malignancies

Author

McKerrell, Thomas, Moreno, Thaidy, Ponstingl, Hannes, Bolli, Niccolo, Dias, João M.L., Tischler, German, Colonna, Vincenza, Manasse, Bridget, Bench, Anthony, Bloxham, David, Herman, Bram, Fletcher, Danielle, Park, Naomi, Quail, Michael A., Manes, Nicla, Hodkinson, Clare, Baxter, Joanna, Sierra, Jorge, Foukaneli, Theodora, Warren, Alan J., Chi, Jianxiang, Costeas, Paul, Rad, Roland, Huntly, Brian, Grove, Carolyn, Ning, Zemin, Tyler-Smith, Chris, Varela, Ignacio, Scott, Mike, Nomdedeu, Josep, Mustonen, Ville, and Vassiliou, George S.

Published
2016
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16. Evolution in the frontline treatment of patients with chronic lymphocytic leukemia: experience from one European center.

Author

Arguello-Tomas, Miguel, Albiol, Nil, Jara, Paola, Garcia-Cadenas, Irene, Redondo, Sara, Esquirol, Albert, Novelli, Silvana, Saavedra, Silvana, Martino, Rodrigo, Nomdedeu, Josep, Sierra, Jordi, Mora, Alba, and Moreno, Carol

Subjects
CHRONIC lymphocytic leukemia, ALKYLATING agents, GENE targeting, OVERALL survival, CHRONIC leukemia
Abstract

Treatment of chronic lymphocytic leukemia (CLL) has dramatically evolved over the last decades thanks to the introduction of targeted therapies. We aimed to describe retrospectively the evolution in the frontline prescription in the CLL patients from our institution. As a secondary objective, the impact of frontline therapy on the time-to-next-treatment (TTNT) and overall survival (OS). After a median of 6.4 years (0.1–36.4) of follow-up from diagnosis, 323 of 780 CLL patients (41.4%) required therapy. Alkylating agents in monotherapy (chlorambucil) were the most used until 2012, and from then, chemoimmunotherapy. Since 2018, targeted therapies were the most common therapeutic strategy (74.1%). Patients who received targeted therapies had significantly longer TTNT compared to other regimens. In the multivariable analyses, mutated IGHV genes targeted therapies and chemoimmunotherapy regimens were related to longer TTNT, and sex female, age younger than 65, and mutated IGHV genes were associated with better OS. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia

Author

Rossi, Davide, Rasi, Silvia, Spina, Valeria, Bruscaggin, Alessio, Monti, Sara, Ciardullo, Carmela, Deambrogi, Clara, Khiabanian, Hossein, Serra, Roberto, Bertoni, Francesco, Forconi, Francesco, Laurenti, Luca, Marasca, Roberto, Dal-Bo, Michele, Rossi, Francesca Maria, Bulian, Pietro, Nomdedeu, Josep, Del Poeta, Giovanni, Gattei, Valter, Pasqualucci, Laura, Rabadan, Raul, Foà, Robin, Dalla-Favera, Riccardo, and Gaidano, Gianluca

Published
2013
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18. Many signs, one mutation: Early onset of de novo GATA2 deficiency syndrome. A case report

Author

Blanco, Maria Laura, Torrent, Montserrat, Bussaglia, Elena, Badell Serra, Isabel, Nomdedeu, Josep, and Universitat Autònoma de Barcelona

Subjects
Pediatrics, medicine.medical_specialty, Medicine (General), Case Report, Case Reports, 030204 cardiovascular system & hematology, Deafness, 03 medical and health sciences, Broad spectrum, 0302 clinical medicine, R5-920, hemic and lymphatic diseases, deafness, warts, medicine, otorhinolaryngologic diseases, GATA2, Lymphedema, Early onset, GATA2 Deficiency, business.industry, General Medicine, lymphedema, medicine.disease, myelodysplastic syndrome, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Medicine, Warts, business, Myelodysplastic syndrome
Abstract

We report a case with a broad spectrum of symptoms, related to GATA2 deficiency syndrome, which emerged as early as at 6 months of age. They ranged from lymphedema, deafness to myelodysplastic syndrome (MDS)., Non‐hematologic symptoms may long precede myelodysplastic syndrome diagnosis in patients with GATA2 mutations.

Published
2020

19. The Notch/Hes1 Pathway Sustains NF-κB Activation through CYLD Repression in T Cell Leukemia

Author

Espinosa, Lluis, Cathelin, Severine, D'Altri, Teresa, Trimarchi, Thomas, Statnikov, Alexander, Guiu, Jordi, Rodilla, Veronica, Inglés-Esteve, Julia, Nomdedeu, Josep, Bellosillo, Beatriz, Besses, Carles, Abdel-Wahab, Omar, Kucine, Nicole, Sun, Shao-Cong, Song, Guangchan, Mullighan, Charles C., Levine, Ross L., Rajewsky, Klaus, Aifantis, Iannis, and Bigas, Anna

Published
2010
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20. An analysis of the impact of CD56 expression in de novo acute promyelocytic leukemia patients treated with upfront all-trans retinoic acid and anthracycline-based regimens

Author

Sobas, Marta, Montesinos, Pau, Boluda, Blanca, Bernal, Teresa, Vellenga, Edo, Nomdedeu, Josep, Gonzalez-Campos, Jose, Chillon, Maria, Holowiecka, Aleksandra, Esteve, Jordi, Bergua, Juan, David Gonzalez-Sanmiguel, Jose, Gil-Cortes, Cristina, Tormo, M., Salamero, Olga, Manso, Felix, Fernandez, Isolda, de la Serna, Javier, Moreno, Maria-Jose, Perez-Encinas, Manuel, Krsnik, Isabel, Ribera, Josep-Maria, Escoda, Lourdes, Lowenberg, Bob, Angel Sanz, Miguel, Beltran de Heredia, J. M., Hernandez, J. M., Arias, J., Ramos, F., Roman, A., de la Serna, J., Negri, S., Rayon, C., Esteve, J., Fernandez-Calvo, F. J., Diaz-Mediavilla, J., Gil, C., Olave, M., Amutio, E., Pedro, C., Gorosquieta, A., Viguria, M., Zudaire, M., Molero, T., Sayas, M. J., Guardia, R., Martinez, J., de Groot, M. R., Schouten, H. C., Hematology, Radiotherapy, Erasmus MC other, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), Interne Geneeskunde, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and MUMC+: MA Hematologie (9)

Subjects
Male, Cancer Research, medicine.medical_treatment, Retinoic acid, CD34, Gene Expression, Kaplan-Meier Estimate, chemotherapy, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, PROGNOSTIC-FACTORS, Leukemia, Promyelocytic, Acute, Recurrence, Acute promyelocytic leukemia, Antineoplastic Combined Chemotherapy Protocols, FAILURE, Anthracyclines, Cumulative incidence, ATRA, Child, CONSOLIDATION, relapse, RISK, Hematology, Middle Aged, Prognosis, CD56 Antigen, Leukemia, Treatment Outcome, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, CD56, medicine.medical_specialty, Adolescent, Anthracycline, Tretinoin, Young Adult, 03 medical and health sciences, ADULT, Internal medicine, medicine, Humans, INDICATOR, Aged, Chemotherapy, business.industry, De novo acute, medicine.disease, chemistry, business, prognostic, 030215 immunology
Abstract

Out of 956, there were 95 (10%) CD56+ APL patients treated with PETHEMA ATRA and chemotherapy. CD56+ expression was associated with high WBC, BCR3 isoform, and co-expression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. CD56+ vs CD56- APL presented higher induction death rate (16% vs 8%, p = .02) and 5-years cumulative incidence of relapse (33% versus 10%, p = .006), irrespectively of the Sanz score (low-risk 47% versus 5%, p

Published
2019
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22. Diverse real-life outcomes after intensive risk-adapted therapy for 1034 AML patients from the CETLAM Group

Author

Oñate, Guadalupe, Garrido, Ana, Arnan, Montserrat, Pomares, Helena, Alonso, Ester, Tormo, Mar, Diaz-Beya, Marina, Vives, Susana, Zamora, Lurdes, Sampol, Antonia, Coll, Rosa, Salamero, Olga, Cervera, Marta, Garcia, Antoni, Vall-Llovera, Ferran, Garcia-Avila, Sara, Bargay, Joan, Ortin, Xavier, Iranzo, Eva, Guijarro, Francisca, Pratcorona, Marta, Nomdedeu, Josep F., Esteve, Jordi, and Sierra, Jorge

Published
2025
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29. Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia.

Author

Ramos-Muntada, Mireia, Trincado, Juan L., Blanco, Joan, Bueno, Clara, Rodríguez-Cortez, Virginia C., Bataller, Alex, López-Millán, Belén, Schwab, Claire, Ortega, Margarita, Velasco, Pablo, Blanco, Maria L., Nomdedeu, Josep, Ramírez-Orellana, Manuel, Minguela, Alfredo, Fuster, Jose L., Cuatrecasas, Esther, Camós, Mireia, Ballerini, Paola, Escherich, Gabriele, and Boer, Judith

Abstract

B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B-ALL. Although hyperdiploidy represents an important prognostic factor in childhood B-ALL, the specific chromosome gains with prognostic value in HHD-B-ALL remain controversial, and the current knowledge about the hierarchy of chromosome gains, clonal heterogeneity and chromosomal instability in HHD-B-ALL remains very limited. We applied automated sequential-iFISH coupled with single-cell computational modeling to identify the specific chromosomal gains of the eight typically gained chromosomes in a large cohort of 72 primary diagnostic (DX, n = 62) and matched relapse (REL, n = 10) samples from HHD-B-ALL patients with either favorable or unfavorable clinical outcome in order to characterize the clonal heterogeneity, specific chromosome gains and clonal evolution. Our data show a high degree of clonal heterogeneity and a hierarchical order of chromosome gains in DX samples of HHD-B-ALL. The rates of specific chromosome gains and clonal heterogeneity found in DX samples differ between HHD-B-ALL patients with favorable or unfavorable clinical outcome. In fact, our comprehensive analyses at DX using a computationally defined risk predictor revealed low levels of trisomies +18+10 and low levels of clonal heterogeneity as robust relapse risk factors in minimal residual disease (MRD)-negative childhood HHD-B-ALL patients: relapse-free survival beyond 5 years: 22.1% versus 87.9%, P < 0.0001 and 33.3% versus 80%, P < 0.0001, respectively. Moreover, longitudinal analysis of matched DX-REL HHD-B-ALL samples revealed distinct patterns of clonal evolution at relapse. Our study offers a reliable prognostic sub-stratification of pediatric MRD-negative HHD-BALL patients. [ABSTRACT FROM AUTHOR]

Published
2022
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31. Genomic lesions associated with a different clinical outcome in diffuse large B-Cell lymphoma treated with R-CHOP-21

Author

Scandurra, Marta, Mian, Michael, Greiner, Timothy C., Rancoita, Paola M. V., De Campos, Cassio P., Chan, Wing C., Vose, Julie M., Chigrinova, Ekaterina, Inghirami, Giorgio, Chiappella, Annalisa, Baldini, Luca, Ponzoni, Maurilio, Ferreri, Andres J.M., Franceschetti, Silvia, Gaidano, Gianluca, Montes-Moreno, Santiago, Piris, Miguel A., Facchetti, Fabio, Tucci, Alessandra, Nomdedeu, Josep Fr., Lazure, Thierry, Lambotte, Olivier, Uccella, Silvia, Pinotti, Graziella, Pruneri, Giancarlo, Martinelli, Giovanni, Young, Ken H., Tibiletti, Maria Grazia, Rinaldi, Andrea, Zucca, Emanuele, Kwee, Ivo, and Bertoni, Francesco

Published
2010
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34. Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone

Author

Sanchez, Maria-Luz, Almeida, Julia, Gonzalez, David, Gonzalez, Marcos, Garcia-Marcos, Maria-Antonia, Balanzategui, Ana, Lopez-Berges, Maria-Consuelo, Nomdedeu, Josep, Vallespi, Teresa, Barbon, Marcos, Martin, Alejandro, de la Fuente, Pilar, Martin-Nuñez, Guillermo, Fernandez-Calvo, Javier, Hernandez, Jesus-Maria, Miguel, Jesus F. San, and Orfao, Alberto

Published
2003
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35. Focal Adhesion Genes Refine the Intermediate-Risk Cytogenetic Classification of Acute Myeloid Leukemia

Author

Pallarès, Victor, Hoyos Colell, Montserrat, Chillón, M. Carmen, Barragán, Eva, Prieto Conde, M. Isabel, Llop, Marta, Falgàs, Aïda, Céspedes, María Virtudes, Montesinos, Pau, Nomdedeu, Josep, Brunet, Salut, Sanz, Miguel Ángel, González-Díaz, Marcos, Sierra, Jorge, Mangues, Ramon, Casanova Rigat, Isolda, Universitat Autònoma de Barcelona, Instituto de Salud Carlos III, European Commission, Fundació La Marató de TV3, Josep Carreras Leukemia Foundation, Asociación Española Contra el Cáncer, Generalitat de Catalunya, and Sociedad Española de Hematología y Hemoterapia

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, NPM1, PTK2, acute myeloid leukemia, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, PTK2B, LYN, Internal medicine, hemic and lymphatic diseases, medicine, prognostic factor, Prognostic factor, intermediate-risk, Acute myeloid leukemia, business.industry, Myeloid leukemia, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, Intermediate-risk, business, Tyrosine kinase, Proto-oncogene tyrosine-protein kinase Src
Abstract

© 2018 by the authors., In recent years, several attempts have been made to identify novel prognostic markers in patients with intermediate-risk acute myeloid leukemia (IR-AML), to implement risk-adapted strategies. The non-receptor tyrosine kinases are proteins involved in regulation of cell growth, adhesion, migration and apoptosis. They associate with metastatic dissemination in solid tumors and poor prognosis. However, their role in haematological malignancies has been scarcely studied. We hypothesized that PTK2/FAK, PTK2B/PYK2, LYN or SRC could be new prognostic markers in IR-AML. We assessed PTK2, PTK2B, LYN and SRC gene expression in a cohort of 324 patients, adults up to the age of 70, classified in the IR-AML cytogenetic group. Univariate and multivariate analyses showed that PTK2B, LYN and PTK2 gene expression are independent prognostic factors in IR-AML patients. PTK2B and LYN identify a patient subgroup with good prognosis within the cohort with non-favorable FLT3/NPM1 combined mutations. In contrast, PTK2 identifies a patient subgroup with poor prognosis within the worst prognosis cohort who display non-favorable FLT3/NPM1 combined mutations and underexpression of PTK2B or LYN. The combined use of these markers can refine the highly heterogeneous intermediate-risk subgroup of AML patients, and allow the development of risk-adapted post-remission chemotherapy protocols to improve their response to treatment.Pallarès, Victor, This work was supported by Instituto de Salud Carlos III (Co-funding from FEDER) [CD13/00074 to V.P., PI15/00378 and PIE15/00028 to R.M., FIS PI17/01246, RD12/0036/0071 and FIS PI14/00450 to J.S., RD12/0036/0069 to M.G.., ISCIII-PS13/1640 and PI16/0665 to E.B., and RD12/0036/0014 and PIE13/00046 to M.A.S.] CIBERONC [CB16/12/00284 to M.A.S.]; CIBER-BBN [CBV6/01/1031 and Nanomets3 to R.M.]; AGAUR [2017 FI_B 00680 to A.F.; 2017-SGR-865 and 2014PROD0005 to R.M. and 2014-SGR-1281 to J.S.]; Fundació La Marató TV3 [416/C/2013-2030 to R.M., 100830/31/32 to J.S., M.G.. and M.A.S.]; Josep Carreras Leukemia Research Institute [P/AG 2017 to R.M.]; Spanish Health Research Program [PI12/02321 to M.G..]; Spanish Association Against Cancer (AECC) [to M.C.C.]; a grant from the Cellex Foundation, Barcelona [to J.S.]; a grant from La Generalitat de Catalunya (PERIS) [SLT002/16/00433 to J.S.]; and a grant from Fundación Española de Hematología y Hemoterapia (FEHH) [to V.P.].

Published
2018
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39. Distribution and pattern of BCL-6 mutations throughout the spectrum of B-cell neoplasia

Author

Capello, Daniela, Vitolo, Umberto, Pasqualucci, Laura, Quattrone, Silvia, Migliaretti, Giuseppe, Fassone, Lucia, Ariatti, Cristiano, Vivenza, Daniela, Gloghini, Annunziata, Pastore, Cristina, Lanza, Carlo, Nomdedeu, Josep, Botto, Barbara, Freilone, Roberto, Buonaiuto, Daniela, Zagonel, Vittorina, Gallo, Eugenio, Palestro, Giorgio, Saglio, Giuseppe, Dalla-Favera, Riccardo, Carbone, Antonino, and Gaidano, Gianluca

Published
2000
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41. Acute myeloid leukemia with NPM1 mutation and favorable European LeukemiaNet category: outcome after preemptive intervention based on measurable residual disease.

Author

Bataller, Alex, Oñate, Guadalupe, Diaz‐Beyá, Marina, Guijarro, Francesca, Garrido, Ana, Vives, Susana, Tormo, Mar, Arnan, Montserrat, Salamero, Olga, Sampol, Antònia, Coll, Rosa, Vall‐Llovera, Ferran, Oliver‐Caldés, Aina, López‐Guerra, Mònica, Pratcorona, Marta, Zamora, Lurdes, Villamon, Eva, Roué, Gaël, Blanco, Adoración, and Nomdedeu, Josep F.

Subjects
ACUTE myeloid leukemia, STEM cell transplantation, PRELEUKEMIA
Abstract

Summary: In the European LeukemiaNet favourable risk category, allogeneic haematopoietic stem cell transplantation (alloSCT) is not indicated in first complete remission for patients with acute myeloid leukaemia (AML) with NPM1 mutations (ELNfav NPM1 AML), although a proportion of these patients will relapse. Given the prognostic importance of measurable residual disease (MRD), CETLAM‐12 considered a pre‐emptive intervention in patients with molecular failure (MF). We analyzed 110 ELNfav NPM1 AML patients achieving complete remission (CR) after induction chemotherapy. Two‐year cumulative incidence of relapse (CIR), overall survival (OS) and leukaemia‐free survival (LFS) were 17%, 81·5% and 82%, respectively. Forty‐six patients required additional therapy for MF (n = 33) or haematological relapse (HemR; n = 13), resulting in a molecular LFS (molLFS) and a cumulative incidence of MF at two years of 61% and 38% respectively. Two‐year OS for these 46 patients was 66%, with a different outcome between patients with MF (86%) and HemR (42%) (P = 0·002). Quantitative NPM1 detection at different timepoints was predictive of molLFS; an MRD ratio (NPM1mut/ABL1 × 100) cut‐off of 0·05 after first consolidation identified two cohorts with a two‐year molLFS of 77% and 40% for patients below and above 0·05, respectively. In conclusion, MRD‐based pre‐emptive intervention resulted in a favourable outcome for ELNfav NPM1 AML patients. [ABSTRACT FROM AUTHOR]

Published
2020
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42. Gene expression workflow to analyze residual leukemic cells in Chronic Lymphocytic Leukemia.

Author

Mora, Alba, Bosch, Rosa, Cuellar‐García, Carolina, Blanco, Laura, Sierra, Jorge, Nomdedeu, Josep, and Moreno, Carol

Subjects
CARCINOGENESIS, CHRONIC lymphocytic leukemia, FLOW cytometry, GENE expression, LEUCOCYTES, OLIGONUCLEOTIDE arrays, GENE expression profiling
Abstract

Background: In chronic lymphocytic leukemia, a better understanding of leukemic cell characteristics after treatment would help to design specific therapeutic approaches aimed at preventing clinical relapse. Gene arrays have become a powerful approach to perform gene expression profiling; nevertheless, to work with residual cells entails an intensive labor. The aim of this study was to set forth an effective gene expression approach to analyze residual leukemic cells. Methods: Leukocytes from CLL patient's samples were sorted by flow cytometry using a 6‐color panel. The quality and quantity of RNA isolated from different inputs of cells were compared by two silica column protocols: RNeasy Micro and RNeasy Mini. RNA amplifications were carried out according to two manufacturer's protocols: Ovation Pico SL and Ovation Pico WTA. A total of 3.5 μg of cDNA was labeled and hybridized to Human Gene 2.0 ST arrays. Results: RNA extracted from low number of input cells by RNeasy Micro showed similar RNA integrity number to that obtained from RNeasy Mini; however, the RNA quantity was higher using the RNeasy Micro Kit. In addition, those RNA samples obtained with RNeasy Micro and amplified with Ovation Pico WTA showed good quality to proceed for a gene array study, independently of the number of input cells (range: 1 × 104‐5 × 105 cells). Conclusions: We observed that this workflow is a feasible approach to obtain genomic material extracted from leukemic cells as little as 1 × 104 cells and it can be useful to carry out gene expression profile experiments to characterize residual leukemic cells in chronic lymphocytic leukemia. [ABSTRACT FROM AUTHOR]

Published
2020
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45. P718: EPIGENOME PROFILING REVEALS ABERRANT DNA METHYLATION SIGNATURE IN GATA2 DEFICIENCY.

Author

Marin‐Bejar, Oskar, Romero‐Moya, Damia, Rodriguez‐Ubreva, Javier, Distefano, Maximiliano, Lessi, Francesca, Aretini, Paolo, Liquori, Alessandro, Castaño, Julio, Kozyra, Emilia, Kotmayer, Lili, Bueno, Clara, Cervera, José, Carlos Rodriguez‐Gallego, José, F Nomdedeu, Josep, Murillo‐Sanjuán, Laura, Díaz de Heredia, Cristina, Pérez‐Martinez, Antonio, López‐Cardenas, Félix, Martínez‐Laperche, Carolina, and Dorado‐Herrero, Nieves

Published
2023
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46. P703: THE AIPSS‐MDS MACHINE LEARNING MODEL PREDICTS OVERALL SURVIVAL AND LEUKEMIC TRANSFORMATION IN CMML: AN ANALYSIS OF THE SPANISH REGISTRY OF MDS.

Author

Mosquera‐Orgueira, Adrian, Mateo Perez Encinas, Manuel, Diaz Varela, Nicolas, Wang, Yu‐Hung, Mora, Elvira, Diaz‐Beya, Marina, Julia Montoro, Maria, Pomares Marin, Helena, Ramos Ortega, Fernando, Tormo, Mar, Jerez, Andres, Nomdedeu, Josep, de Migue Sanchez, Carlos, Arenillas, Leonor, Carcel, Paula, Teresa Cedena Romero, Maria, Xicoy Cirici, Blanca, Rivero Arango, Eugenia, Andrés Del Orbe Barreto, Rafael, and Benlloch, Luis

Published
2023
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47. Molecular profiling refines minimal residual disease‐based prognostic assessment in adults with Philadelphia chromosome‐negative B‐cell precursor acute lymphoblastic leukemia.

Author

Ribera, Jordi, Zamora, Lurdes, Morgades, Mireia, Vives, Susana, Granada, Isabel, Montesinos, Pau, Gómez‐Seguí, Inés, Mercadal, Santiago, Guàrdia, Ramon, Nomdedeu, Josep, Pratcorona, Marta, Tormo, Mar, Martínez‐Lopez, Joaquín, Hernández‐Rivas, Jesús‐María, Ciudad, Juana, Orfao, Alberto, González‐Campos, José, Barba, Pere, Escoda, Lourdes, and Esteve, Jordi

Published
2019
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48. The poor prognosis of low hypodiploidy in adults with B‐cell precursor acute lymphoblastic leukaemia is restricted to older adults and elderly patients.

Author

Ribera, Jordi, Granada, Isabel, Morgades, Mireia, Vives, Susana, Genescà, Eulàlia, González, Celia, Nomdedeu, Josep, Escoda, Lourdes, Montesinos, Pau, Mercadal, Santiago, Coll, Rosa, González‐Campos, José, Abella, Eugenia, Barba, Pere, Bermúdez, Arancha, Gil, Cristina, Tormo, Mar, Pedreño, María, Martínez‐Carballeira, Daniel, and Hernández‐Rivas, Jesús‐María

Subjects
OLDER people, OLDER patients, ADULTS, PROGNOSIS
Abstract

Summary: The prognostic significance of low‐hypodiploidy has not been extensively evaluated in minimal residual disease (MRD)‐oriented protocols for adult acute lymphoblastic leukaemia (ALL). We analysed the outcome of hypodiploid adult ALL patients treated within Programa Español de Tratamientos en Hematología (PETHEMA) protocols. The 5‐year cumulative incidence of relapse (CIR) of low‐hypodiploid B‐cell precursor (BCP)‐ALL was significantly higher than that of high‐hypodiploids (52% vs. 12%, P = 0.013). Low‐hypodiploid BCP‐ALL patients aged ≤35 years showed superior survival (71% vs. 21%, P = 0.026) and lower 5‐year CIR (17% vs. 66%, P = 0.090) than low‐hypodiploids aged >35 years. Older adults and elderly low‐hypodiploid BCP‐ALL patients show dismal prognosis although achieving an end‐induction good MRD response. [ABSTRACT FROM AUTHOR]

Published
2019
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50. A 4-gene expression prognostic signature might guide post-remission therapy in patients with intermediate-risk cytogenetic acute myeloid leukemia.

Author

Torrebadell, Montserrat, Díaz-Beyá, Marina, Kalko, Susana G., Pratcorona, Marta, Nomdedeu, Josep, Navarro, Alfons, Gel, Bernat, Brunet, Salut, Sierra, Jorge, Camós, Mireia, and Esteve, Jordi

Subjects
ACUTE myeloid leukemia, HEMATOPOIETIC stem cells, GENES, GENE expression, GENETICS
Abstract

In intermediate-risk cytogenetic acute myeloid leukemia (IRC-AML) patients, novel biomarkers to guide post-remission therapy are needed. We analyzed with high-density arrays 40 IRC-AML patients who received a non-allogeneic hematopoietic stem-cell transplantation-based post-remission therapy, and identified a signature that correlated with early relapse. Subsequently, we analyzed selected 187 genes in 49 additional IRC-AML patients by RT-PCR. BAALC, MN1, SPARC and HOPX overexpression correlated to refractoriness. BAALC or ALDH2 overexpression correlated to shorter overall survival (OS) (5-year OS: 33 ± 8.6% vs. 73.7 ± 10.1%, p = .006; 32 ± 9.3% vs. 66.4 ± 9.7%, p = .016), whereas GPR44 or TP53INP1 overexpression correlated to longer survival (5-year OS: 66.7 ± 10.3% vs. 35.4 ± 9.1%, p = .04; 58.3 ± 8.2% vs. 23.1 ± 11.7%, p = .029). A risk-score combining these four genes expression distinguished low-risk and high-risk patients (5-year OS: 79 ± 9% vs. 30 ± 8%, respectively; p = .001) in our cohort and in an independent set of patients from a public repository. Our 4-gene signature may add prognostic information and guide post-remission treatment in IRC-AML patients. [ABSTRACT FROM AUTHOR]

Published
2018
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