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2. Review on imidacloprid diffusion route and a case study: from apple orchard to the honey bee colony matrices.

Author

MALAGNINI, Valeria, FONTANA, Paolo, DI PRISCO, Gennaro, MEDRZYCKI, Piotr, ZANOTELLI, Livia, POWER, Karen, COLOMBO, Roberto, SERRA, Giorgia, BOI, Michela, and ANGELI, Gino

Abstract

Honey bees play a pivotal role in natural and rural ecosystems by providing human and animal food sources through pollination services. However, in cultivated areas, they can be exposed to the chemicals utilized for crop protection. Neonicotinoid insecticides can adversely affect honey bee colonies impairing their survival, immunity and biological activities at lethal and sublethal doses. For this reason, neonicotinoids, together with other stress factors, like pathogens (e.g. viruses and Varroa mites), climate change and food shortage, are considered one of the causes of worldwide colony losses. Nevertheless, the natural way of entry and diffusion of these pesticides in field colonies is not completely clear. Here, we wanted to fill this gap by studying the diffusion route of imidacloprid and its metabolites by analysing different matrices collected from honey bee colonies used for pollination of apple orchards, in the framework of applied Integrated Pest Management strategies. Pollen, honey bees, honey, royal jelly, bee wax and bee bread were sampled from 6 honey bee colonies placed in two different apple orchards before blooming, exposed to chemicals application and removed from the site after that. Samples were analysed using a liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) in order to detect imidacloprid, olefin imidacloprid and 5-hydroxy imidacloprid. The results demonstrate that the primary way of entrance of imidacloprid was the pollen transported by foragers, while the main accumulation matrices were bee bread, honey and wax. These findings allow us to hypothesize that the accumulation of this insecticide, especially in bee bread, the main larval food, could potentially impact negatively on honey bee wellbeing at the adult stage. Moreover, our data could implement the honey bee colony simulator. [ABSTRACT FROM AUTHOR]

Published
2023

3. Supplemental Table S4 from The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs

Author

Boi, Michela, primary, Gaudio, Eugenio, primary, Bonetti, Paola, primary, Kwee, Ivo, primary, Bernasconi, Elena, primary, Tarantelli, Chiara, primary, Rinaldi, Andrea, primary, Testoni, Monica, primary, Cascione, Luciano, primary, Ponzoni, Maurilio, primary, Mensah, Afua Adjeiwaa, primary, Stathis, Anastasios, primary, Stussi, Georg, primary, Riveiro, María Eugenia, primary, Herait, Patrice, primary, Inghirami, Giorgio, primary, Cvitkovic, Esteban, primary, Zucca, Emanuele, primary, and Bertoni, Francesco, primary

Published
2023
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4. Supplemental Figures S1-2 from The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs

Author

Boi, Michela, primary, Gaudio, Eugenio, primary, Bonetti, Paola, primary, Kwee, Ivo, primary, Bernasconi, Elena, primary, Tarantelli, Chiara, primary, Rinaldi, Andrea, primary, Testoni, Monica, primary, Cascione, Luciano, primary, Ponzoni, Maurilio, primary, Mensah, Afua Adjeiwaa, primary, Stathis, Anastasios, primary, Stussi, Georg, primary, Riveiro, María Eugenia, primary, Herait, Patrice, primary, Inghirami, Giorgio, primary, Cvitkovic, Esteban, primary, Zucca, Emanuele, primary, and Bertoni, Francesco, primary

Published
2023
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5. Supplemental Figures S6 from The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs

Author

Boi, Michela, primary, Gaudio, Eugenio, primary, Bonetti, Paola, primary, Kwee, Ivo, primary, Bernasconi, Elena, primary, Tarantelli, Chiara, primary, Rinaldi, Andrea, primary, Testoni, Monica, primary, Cascione, Luciano, primary, Ponzoni, Maurilio, primary, Mensah, Afua Adjeiwaa, primary, Stathis, Anastasios, primary, Stussi, Georg, primary, Riveiro, María Eugenia, primary, Herait, Patrice, primary, Inghirami, Giorgio, primary, Cvitkovic, Esteban, primary, Zucca, Emanuele, primary, and Bertoni, Francesco, primary

Published
2023
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6. Supplemental Table S2-3 from The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs

Author

Boi, Michela, primary, Gaudio, Eugenio, primary, Bonetti, Paola, primary, Kwee, Ivo, primary, Bernasconi, Elena, primary, Tarantelli, Chiara, primary, Rinaldi, Andrea, primary, Testoni, Monica, primary, Cascione, Luciano, primary, Ponzoni, Maurilio, primary, Mensah, Afua Adjeiwaa, primary, Stathis, Anastasios, primary, Stussi, Georg, primary, Riveiro, María Eugenia, primary, Herait, Patrice, primary, Inghirami, Giorgio, primary, Cvitkovic, Esteban, primary, Zucca, Emanuele, primary, and Bertoni, Francesco, primary

Published
2023
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7. Supplemental Figures S3-5 from The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs

Author

Boi, Michela, primary, Gaudio, Eugenio, primary, Bonetti, Paola, primary, Kwee, Ivo, primary, Bernasconi, Elena, primary, Tarantelli, Chiara, primary, Rinaldi, Andrea, primary, Testoni, Monica, primary, Cascione, Luciano, primary, Ponzoni, Maurilio, primary, Mensah, Afua Adjeiwaa, primary, Stathis, Anastasios, primary, Stussi, Georg, primary, Riveiro, María Eugenia, primary, Herait, Patrice, primary, Inghirami, Giorgio, primary, Cvitkovic, Esteban, primary, Zucca, Emanuele, primary, and Bertoni, Francesco, primary

Published
2023
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8. Convergent Mutations and Kinase Fusions Lead to Oncogenic STAT3 Activation in Anaplastic Large Cell Lymphoma

Author

Crescenzo, Ramona, Abate, Francesco, Lasorsa, Elena, Tabbo’, Fabrizio, Gaudiano, Marcello, Chiesa, Nicoletta, Di Giacomo, Filomena, Spaccarotella, Elisa, Barbarossa, Luigi, Ercole, Elisabetta, Todaro, Maria, Boi, Michela, Acquaviva, Andrea, Ficarra, Elisa, Novero, Domenico, Rinaldi, Andrea, Tousseyn, Thomas, Rosenwald, Andreas, Kenner, Lukas, Cerroni, Lorenzo, Tzankov, Alexander, Ponzoni, Maurilio, Paulli, Marco, Weisenburger, Dennis, Chan, Wing C., Iqbal, Javeed, Piris, Miguel A., Zamo’, Alberto, Ciardullo, Carmela, Rossi, Davide, Gaidano, Gianluca, Pileri, Stefano, Tiacci, Enrico, Falini, Brunangelo, Shultz, Leonard D., Mevellec, Laurence, Vialard, Jorge E., Piva, Roberto, Bertoni, Francesco, Rabadan, Raul, and Inghirami, Giorgio

Published
2015
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9. PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma

Author

Boi, Michela, Rinaldi, Andrea, Kwee, Ivo, Bonetti, Paola, Todaro, Maria, Tabbò, Fabrizio, Piva, Roberto, Rancoita, Paola M.V., Matolcsy, András, Timar, Botond, Tousseyn, Thomas, Rodríguez-Pinilla, Socorro Maria, Piris, Miguel A., Beà, Sílvia, Campo, Elias, Bhagat, Govind, Swerdlow, Steven H., Rosenwald, Andreas, Ponzoni, Maurilio, Young, Ken H., Piccaluga, Pier Paolo, Dummer, Reinhard, Pileri, Stefano, Zucca, Emanuele, Inghirami, Giorgio, and Bertoni, Francesco

Published
2013
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10. Telomere loss in Philadelphia-negative hematopoiesis after successful treatment of chronic myeloid leukemia: Evidence for premature aging of the myeloid compartment

Author

Lobetti-Bodoni, Chiara, Ferrero, Dario, Genuardi, Elisa, Passera, Roberto, Bernocco, Elisa, Sia, Daniela, Grignani, Giovanni, Crisà, Elena, Monitillo, Luigia, Rocci, Alberto, Drandi, Daniela, Giai, Valentina, Zanni, Manuela, Boi, Michela, Isaia, Gianluca, Barbero, Daniela, Lunghi, Monia, Abruzzese, Elisabetta, Radaelli, Franca, Pini, Massimo, Pregno, Patrizia, Carlo-Stella, Carmelo, Gaidano, Gianluca, Boccadoro, Mario, and Ladetto, Marco

Published
2012
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13. Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts

Author

Scarfò, Irene, Pellegrino, Elisa, Mereu, Elisabetta, Kwee, Ivo, Agnelli, Luca, Bergaggio, Elisa, Garaffo, Giulia, Vitale, Nicoletta, Caputo, Manuel, Machiorlatti, Rodolfo, Circosta, Paola, Abate, Francesco, Barreca, Antonella, Novero, Domenico, Mathew, Susan, Rinaldi, Andrea, Tiacci, Enrico, Serra, Sara, Deaglio, Silvia, Neri, Antonino, Falini, Brunangelo, Rabadan, Raul, Bertoni, Francesco, Inghirami, Giorgio, Piva, Roberto, Boi, Michela, Crescenzo, Ramona, Cuccuru, Giuditta, Gaudiano, Marcello, Lasorsa, Elena, Medico, Enzo, Messana, Katia, Spaccarotella, Elisa, Tabbò, Fabrizio, Todaro, Maria, Fornari, Alessandro, Chilosi, Marco, Zamò, Alberto, Facchetti, Fabio, Lonardi, Silvia, De Chiara, Anna, Fulciniti, Franco, Doglioni, Claudio, Ponzoni, Maurilio, Todoerti, Katia, De Wolf Peeters, Christiane, Tousseyn, Thomas, Van Loo, Peter, Geissinger, Eva, Muller Hermelink, Hans Konrad, Rosenwald, Andreas, Matolcsy, Andras, Piris, Miguel Angel, Rodriguez Pinilla, Maria E., AGOSTINELLI, CLAUDIO, PICCALUGA, PIER PAOLO, PILERI, STEFANO, Scarfò, Irene, Pellegrino, Elisa, Mereu, Elisabetta, Kwee, Ivo, Agnelli, Luca, Bergaggio, Elisa, Garaffo, Giulia, Vitale, Nicoletta, Caputo, Manuel, Machiorlatti, Rodolfo, Circosta, Paola, Abate, Francesco, Barreca, Antonella, Novero, Domenico, Mathew, Susan, Rinaldi, Andrea, Tiacci, Enrico, Serra, Sara, Deaglio, Silvia, Neri, Antonino, Falini, Brunangelo, Rabadan, Raul, Bertoni, Francesco, Inghirami, Giorgio, Piva, Roberto, Boi, Michela, Crescenzo, Ramona, Cuccuru, Giuditta, Gaudiano, Marcello, Lasorsa, Elena, Medico, Enzo, Messana, Katia, Spaccarotella, Elisa, Tabbò, Fabrizio, Todaro, Maria, Fornari, Alessandro, Chilosi, Marco, Zamò, Alberto, Facchetti, Fabio, Lonardi, Silvia, De Chiara, Anna, Fulciniti, Franco, Doglioni, Claudio, Ponzoni, Maurilio, Todoerti, Katia, Agostinelli, Claudio, Piccaluga, Pier Paolo, Pileri, Stefano, De Wolf-Peeters, Christiane, Tousseyn, Thoma, Van Loo, Peter, Geissinger, Eva, Muller-Hermelink, Hans Konrad, Rosenwald, Andrea, Matolcsy, Andra, Piris, Miguel Angel, Rodriguez-Pinilla, Maria E., Scarfò, I, Pellegrino, E, Mereu, E, Kwee, I, Agnelli, L, Bergaggio, E, Garaffo, G, Vitale, N, Caputo, M, Machiorlatti, R, Circosta, P, Abate, F, Barreca, A, Novero, D, Mathew, S, Rinaldi, A, Tiacci, E, Serra, S, Deaglio, S, Neri, A, Falini, B, Rabadan, R, Bertoni, F, Inghirami, G, Piva, R, the European T-Cell Lymphoma Study, Group, Doglioni, C, and Ponzoni, M

Subjects
0301 basic medicine, Untranslated region, Receptor, ErbB-4, Messenger, Mice, SCID, Biochemistry, Mice, 0302 clinical medicine, 5' Untranslated Region, HEK293 Cell, Mutant Protein, Mice, Inbred NOD, hemic and lymphatic diseases, 5' Untranslated RegionsAnimalsCodon, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, NIH 3T3 Cell, Regulation of gene expression, TransgenicMolecular Sequence DataMutant ProteinsNIH 3T3 CellsReceptor Protein-Tyrosine KinasesReceptor, Hematology, Long terminal repeat, Large-Cell, Gene Expression Regulation, Neoplastic, Receptor Protein-Tyrosine Kinase, Codon, Nonsense, 030220 oncology & carcinogenesis, Lymphoma, Large-Cell, Anaplastic, Human, Molecular Sequence Data, Immunology, ErbB-4RNA, Mice, Transgenic, Biology, 03 medical and health sciences, Complementary DNA, Animals, Humans, RNA, Messenger, Gene, NonsenseGene Expression Regulation, NeoplasticHEK293 CellsHumansLymphoma, Animal, Receptor Protein-Tyrosine Kinases, RNA, Cell Biology, Molecular biology, Gene expression profiling, HEK293 Cells, 030104 developmental biology, Inbred NODMice, NIH 3T3 Cells, Mutant Proteins, SCIDMice, AnaplasticMiceMice, 5' Untranslated Regions, 5' Untranslated RegionsAnimalsCodon, NonsenseGene Expression Regulation, NeoplasticHEK293 CellsHumansLymphoma, Large-Cell, AnaplasticMiceMice, Inbred NODMice, SCIDMice, TransgenicMolecular Sequence DataMutant ProteinsNIH 3T3 CellsReceptor Protein-Tyrosine KinasesReceptor, ErbB-4RNA, Messenger
Abstract

Anaplastic large-cell lymphoma (ALCL) is a clinical and biological heterogeneous disease that includes systemic anaplastic lymphoma kinase (ALK)-positive and ALK-negative entities. To discover biomarkers and/or genes involved in ALK-negative ALCL pathogenesis, we applied the cancer outlier profile analysis algorithm to a gene expression profiling data set including 249 cases of T-cell non-Hodgkin lymphoma and normal T cells. Ectopic coexpression of ERBB4 and COL29A1 genes was detected in 24% of ALK-negative ALCL patients. RNA sequencing and 5' RNA ligase-mediated rapid amplification of complementary DNA ends identified 2 novel ERBB4-truncated transcripts displaying intronic transcription start sites. By luciferase assays, we defined that the expression of ERBB4-aberrant transcripts is promoted by endogenous intronic long terminal repeats. ERBB4 expression was confirmed at the protein level by western blot analysis and immunohistochemistry. Lastly, we demonstrated that ERBB4-truncated forms show oncogenic potentials and that ERBB4 pharmacologic inhibition partially controls ALCL cell growth and disease progression in an ERBB4-positive patient-derived tumorgraft model. In conclusion, we identified a new subclass of ALK-negative ALCL characterized by aberrant expression of ERBB4-truncated transcripts carrying intronic 5' untranslated regions. © 2016 by The American Society of Hematology.

Published
2016
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16. Beyond NPM-anaplastic lymphoma kinase driven lymphomagenesis

Author

Fabrizio Tabbò, Maurilio Ponzoni, Raul Rabadan, Francesco Bertoni, Giorgio Inghirami European T. cell Lymphoma Study Group, Aliberti Sabrina, Barreca Antonella, Besson Luca, Crescenzo Ramona, Di Giacomo Filomena, Gaudiano Marcello, Inghirami Giorgio, Landra Indira, Lasorsa Elena, Machiorlatti Rodolfo, Mereu Elisabetta, Messana Katia, Novero Domenico, Pellegrino Elisa, Pich Achille, Piva Roberto, Scarfo Irene, Spaccarotella Elisa, Tabbo Fabrizio, Todaro Maria, Ubezzi Ivana, Urigu Susanna, Vittone Francesco, Abage Francesco, Ficarra Elisa, Acquaviva Andrea, Ponzoni Maurilio, Stella Carmelo, AGOSTINELLI, CLAUDIO, PICCALUGA, PIER PAOLO, PILERI, STEFANO, Falini Brunangelo, Tiacci Enrico, Bertoni Francesco, Boi Michela, Kwee Ivo, Fabrizio Tabbò,Maurilio Ponzoni,Raul Rabadan,Francesco Bertoni,Giorgio Inghirami European T-cell Lymphoma Study Group, Aliberti Sabrina, Barreca Antonella, Besson Luca, Crescenzo Ramona, Di Giacomo Filomena, Gaudiano Marcello, Inghirami Giorgio, Landra Indira, Lasorsa Elena, Machiorlatti Rodolfo, Mereu Elisabetta, Messana Katia, Novero Domenico, Pellegrino Elisa, Pich Achille, Piva Roberto, Scarfo Irene, Spaccarotella Elisa, Tabbo Fabrizio, Todaro Maria, Ubezzi Ivana, Urigu Susanna, Vittone Francesco, Abage Francesco, Ficarra Elisa, Acquaviva Andrea, Ponzoni Maurilio, Stella Carmelo, Agostinelli Claudio, Piccaluga Pier Paolo, Pileri Stefano, Falini Brunangelo, Tiacci Enrico, Bertoni Francesco, Boi Michela, and Kwee Ivo

Subjects
Anaplastic lymphoma kinase, Kinase inhibitor, Signalling pathways, hemic and lymphatic diseases, Lymphoid differentiation, Mouse model
Abstract

PURPOSE OF REVIEW: Anaplastic large cell lymphomas (ALCLs) are rare entities whose somatic genetic lesions have been identified only in a subset of patients. Thus, an integrated and massive discovery programme is required to define their tumourigenic alterations and to design more successful tailored therapies. RECENT FINDINGS: The discovery of anaplastic lymphoma kinase (ALK) fusions has provided the basis for the characterization of distinct subsets among ALCL patients. Although the oncogenic addiction of ALK signalling is proven, the tumorigenic contribution of coactivating lesions is still missing. As ALK- and ALK+ share common signatures, it is plausible that analogous mechanisms of transformation may be operating in both subsets, as confirmed by the dysregulated activation of c-MYC, RAS and NFκB, and the loss of Blimp-1 and p53/p63 axis. Nonetheless, recurrent genetic alterations for ALK- ALCL or refractory leukaemic ALK+ ALCL are lacking. Moreover, although conventional chemotherapies (anthracycline-based) are most successful, that is in ALK+ ALCL patients, the implementation of ALK inhibitors or of anti-CD30 based treatments provides innovative solutions, particularly in paediatric ALK+ ALCL and in chemorefractory/relapsed patients. SUMMARY: The complete portrayal of the landscape of genetic alterations in ALCL will dictate the development of innovative chemotherapeutic and targeted therapies that will fit most with the molecular and clinical profiling of individual patients.

Published
2013

17. Genomic profiling of Anaplastic Large Cell Lymphoma

Author

Boi, Michela, Scapozza, Leonardo, and Bertoni, Francesco

Subjects
BLIMP1, hemic and lymphatic diseases, Genomic, SNP, ddc:500, TP53, ALCL
Abstract

ALCL is one of the most common form of NHL. ALCL has been separated in two distinct entities based on the presence or absence of translocations affecting ALK gene. The aim of this project is to demonstrate that ALK+ and ALK- subsets can definitively be considered different entities. ALK- ALCL samples have a more perturbated and complex profile. Among all the ALCLs, the most common losses affected 17p13.3-p12 (TP53, 25%) and 6q21 (PRDM1, 19%). PRDM1 was inactivated in 12/31 (39%) and in 1/33 (3%) of clinical specimens derived from ALK- and ALK+ ALCL respectively, in 4/7 (57%) ALCL cell lines. We perform gain-of-function experiments in order to unravel the function of BLIMP1 loss in ALCL pathogenesis. After the re-expression of PRDM1, ALCL cells underwent proliferation arrest, with a concomitant moderate increase in the percentage of apoptotic cells and an arrest in cell cycle, suggesting a tumor suppressor role for BLIMP1.

Published
2013

19. Epigenomic evolution in diffuse large B-cell lymphomas

Author

Pan, Heng, primary, Jiang, Yanwen, additional, Boi, Michela, additional, Tabbò, Fabrizio, additional, Redmond, David, additional, Nie, Kui, additional, Ladetto, Marco, additional, Chiappella, Annalisa, additional, Cerchietti, Leandro, additional, Shaknovich, Rita, additional, Melnick, Ari M., additional, Inghirami, Giorgio G., additional, Tam, Wayne, additional, and Elemento, Olivier, additional

Published
2015
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20. The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs

Author

Boi, Michela, primary, Gaudio, Eugenio, additional, Bonetti, Paola, additional, Kwee, Ivo, additional, Bernasconi, Elena, additional, Tarantelli, Chiara, additional, Rinaldi, Andrea, additional, Testoni, Monica, additional, Cascione, Luciano, additional, Ponzoni, Maurilio, additional, Mensah, Afua Adjeiwaa, additional, Stathis, Anastasios, additional, Stussi, Georg, additional, Riveiro, María Eugenia, additional, Herait, Patrice, additional, Inghirami, Giorgio, additional, Cvitkovic, Esteban, additional, Zucca, Emanuele, additional, and Bertoni, Francesco, additional

Published
2015
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21. Convergent Mutations and New Kinase Fusions Lead to Oncogenic STAT3 Activation in Anaplastic Large Cell Lymphoma

Author

Crescenzo, Ramona, primary, Abate, Francesco, additional, Lasorsa, Elena, additional, Tabbo', Fabrizio, additional, Gaudiano, Marcello, additional, Chiesa, Nicoletta, additional, Di Giacomo, Filomena, additional, Spaccarotella, Elisa, additional, Barbarossa, Luigi, additional, Todaro, Maria, additional, Boi, Michela, additional, Tousseyn, Thomas, additional, Rosenwald, Andreas, additional, Kenner, Lukas, additional, Rossi, Davide, additional, Mevellec, Laurence, additional, Vialard, Jorge, additional, Bertoni, Francesco, additional, Rabadan, Raul, additional, and Inghirami, Giorgio, additional

Published
2014
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23. Abstract 5530: OTX015, a novel pan BET-BRD inhibitor is active in non-small-cell lung cancer (NSCLC) cell lines bearing the fusion protein EML4-ALK

Author

Vázquez, Ramiro, primary, Astorgues-Xerri, Lucile, additional, Bekradda, Mohamed, additional, Cvitkovic, Esteban, additional, Herait, Patrice, additional, Boi, Michela, additional, Inghirami, Giorgio, additional, D'Incalci, Maurizio, additional, Riveiro, María E., additional, and Raymond, Eric, additional

Published
2014
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24. Abstract 5531: OTX015, a novel BET inhibitor, is a promising anticancer agent for multiple myeloma

Author

Todaro, Maria, primary, Boi, Michela, additional, Vurchio, Valentina, additional, Ercole, Elisabetta, additional, Machiorlatti, Rodolfo, additional, Messana, Katia, additional, Landra, Indira, additional, Urigu, Susanna, additional, Aliberti, Sabrina, additional, Riveiro, Eugenia, additional, Bertoni, Francesco, additional, and Inghirami, Giorgio, additional

Published
2014
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25. Abstract 5528: The BET Bromodomain inhibitor OTX015 targets the NFKB, TLR and JAK/STAT pathways and shows pre-clinical activity as single agent and in combination in mature B-cell tumors

Author

Gaudio, Eugenio, primary, Bernasconi, Elena, additional, Kwee, Ivo, additional, Boi, Michela, additional, Bonetti, Paola, additional, Tarantelli, Chiara, additional, Rinaldi, Andrea, additional, Testoni, Monica, additional, Ponzoni, Maurilio, additional, Stathis, Anastasios, additional, Stüssi, Georg, additional, Riveiro, Eugenia, additional, Herait, Patrice, additional, Zucca, Emanuele, additional, and Bertoni, Francesco, additional

Published
2014
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26. Genetic Factors Predicting The Response To BET Bromodomain Inhibitors In Lymphoma Lead To New Synergistic Combinations

Author

Gaudio, Eugenio, primary, Kwee, Ivo, additional, Rinaldi, Andrea, additional, Boi, Michela, additional, Bernasconi, Elena, additional, Testoni, Monica, additional, Stathis, Anastasios, additional, Herait, Patrice, additional, Noel, Kay, additional, Inghirami, Giorgio, additional, Zucca, Emanuele, additional, and Bertoni, Francesco, additional

Published
2013
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28. Abstract A119: The BET-bromodomain inhibitor OTX015 shows synergism with several anticancer agents in preclinical models of diffuse large B-cell lymphoma (DLBCL).

Author

Gaudio, Eugenio, primary, Kwee, Ivo, additional, Bernasconi, Elena, additional, Rinaldi, Andrea, additional, Testoni, Monica, additional, Boi, Michela, additional, Stathis, Anastasios, additional, Riveiro, Eugenia, additional, Noel, Kay, additional, Zucca, Emanuele, additional, and Bertoni, Francesco, additional

Published
2013
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29. Abstract 3853: Humanized NOD/Scid/IL2g-/- tumor grafts recapitulate primary anaplastic large cell lymphoma.

Author

Tabbo', Fabrizio, primary, Barreca, Antonella, additional, Machiorlatti, Rodolfo, additional, Messana, Katia, additional, Landra, Indira, additional, Abate, Francesco, additional, Boi, Michela, additional, Todaro, Maria, additional, Abele, Cristina, additional, Novero, Domenico, additional, Zamo', Alberto, additional, Chilosi, Marco, additional, Ponzoni, Maurilio, additional, Cheng, Mangeng, additional, Ruggeri, Bruce, additional, Piccaluga, Pierpaolo, additional, Pileri, Stefano, additional, Tiacci, Enrico, additional, Falini, Brunangelo, additional, Shultz, Lenny, additional, Piva, Roberto, additional, Medico, Enzo, additional, Bertoni, Francesco, additional, Rabadan, Raul, additional, and Inghirami, Giorgio, additional

Published
2013
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30. Abstract 1017: The BRD-inhibitor OTX015 affects proliferation and gene expression of cells derived from mature lymphoid neoplasms.

Author

Bonetti, Paola, primary, Boi, Michela, additional, Bernasconi, Elena, additional, Rinaldi, Andrea, additional, Kwee, Ivo, additional, Gaudio, Eugenio, additional, Ponzoni, Maurilio, additional, Tibiletti, Maria Grazia, additional, Stathis, Anastasios, additional, Riveiro, Eugenia, additional, Inghirami, Giorgio, additional, Zucca, Emanuele, additional, and Bertoni, Francesco, additional

Published
2013
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31. A 10 year survey of acaricide residues in beeswax analysed in Italy.

Author

Boi, Michela, Serra, Giorgia, Colombo, Roberto, Lodesani, Marco, Massi, Sergio, and Costa, Cecilia

Subjects
ACARICIDES, BEESWAX, INSECTICIDE residues, BEEKEEPING, GAS chromatography, VARROA destructor, HONEYBEES
Abstract

BACKGROUND The aim of this work was to provide an overview of the prevalence and level of acaricides in beeswax used in Italy in the past 10 years by analysing 1319 beeswax samples processed by the certified laboratory of the Italian Bee Research Institute. RESULTS The proportion of samples positive to at least one active ingredient decreased between 2005 and 2009 (from 69 to 32%) and then increased again between 2009 and 2014 (from 32 to 91%). This trend is in agreement with reports from beekeepers that the use of synthetic acaricides decreased in the second half of the past decade and increased after the beginning of the colony losses phenomenon. The active ingredient with the greatest overall proportion of positive samples was coumaphos (49%), followed by fluvalinate (38%) and chlorphenvinphos (25%). The indicator for amitraz, 2,4-dimethylphenylformamide ( DMPF), was detected in a very small proportion of samples (6%), while residues of cymiazole were never found. CONCLUSIONS In more than half of the analysed samples, residues of at least one active ingredient were detected. The mean levels of residues of all the considered active ingredients in the positive samples may represent a source of accumulation in beeswax and pose risks to honey bee health. © 2015 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Published
2016
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34. BLIMP1 Is Commonly Inactivated In Anaplastic Large T-Cell Lymphomas (ALCL)

Author

Boi, Michela, primary, Rinaldi, Andrea, additional, Piva, Roberto, additional, Rancoita, Paola MV, additional, Bonetti, Paola, additional, Matolcsy, Andras, additional, Tousseyn, Thomas, additional, Rodríguez-Pinilla, Socorro Maria, additional, Piris, Miguel, additional, Beà, Sílvia, additional, Campo, Elias, additional, Bhagat, Govind, additional, Swerdlow, Steven H., additional, Rosenwald, Andreas, additional, Ponzoni, Maurilio, additional, Young, Ken H., additional, Piccaluga, Pier Paolo, additional, Pileri, Stefano, additional, Neri, Antonino, additional, Medico, Enzo, additional, Zucca, Emanuele, additional, Kwee, Ivo, additional, Inghirami, Giorgio, additional, and Bertoni, Francesco, additional

Published
2011
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35. Severe Telomeric Erosion In Ph-Negative Hematopoiesis After Successful CML Treatment: Association with Acquired Cytogenetic Lesions and Hematological Toxicity.

Author

Bodoni, Chiara Lobetti, primary, Dario, Ferrero, additional, Genuardi, Elisa, additional, Passera, Roberto, additional, Bernocco, Elisa, additional, Daniela, Sia, additional, Crisà, Elena, additional, Grignani, Giovanni, additional, Rocci, Alberto, additional, Monitillo, Luigia, additional, Drandi, Daniela, additional, Giai, Valentina, additional, Ferrero, Simone, additional, Boi, Michela, additional, Mantella, Elisabetta, additional, Isaia, Gianluca, additional, Lunghi, Monia, additional, Abruzzese, Elisabetta, additional, Radaelli, Franca, additional, Pini, Massimo, additional, Pregno, Patrizia, additional, Carlo-Stella, Carmelo, additional, Gaidano, Gianluca, additional, Boccadoro, Mario, additional, and Ladetto, Marco, additional

Published
2010
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36. IGH Repertoire Analysis In Multiple Myeloma (MM): Lack of Intra-Disease Homology and Occasional Clustering with Sequences of Other B-Cell Neoplasms Sharing Identical Geographical Origin

Author

Ferrero, Simone, primary, Capello, Daniela, additional, Svaldi, Mirija, additional, Drandi, Daniela, additional, Boi, Michela, additional, Barbiero, Sara, additional, Gatti, Daniela, additional, Rossi, Davide, additional, Genuardi, Elisa, additional, Antico, Odetta, additional, Ghione, Paola, additional, Zanni, Manuela, additional, Rocci, Alberto, additional, Bertoni, Francesco, additional, Zucca, Emanuele, additional, Gattei, Valter, additional, Palumbo, Antonio, additional, Cortelazzo, Sergio, additional, Boccadoro, Mario, additional, Gaidano, Gianluca, additional, and Ladetto, Marco, additional

Published
2010
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37. Ph-Negative Hematopoiesis Emerging After Successful Treatment of Chronic Myeloid Leukemia Displays Severe and Persistent Telomeric Loss Which Is Particularly Prominent in Patients with Acquired Cytogenetic Abnormalities.

Author

Bodoni, Chiara Lobetti, primary, Ferrero, Dario, additional, Genuardi, Elisa, additional, Sia, Daniela, additional, Genuardi, Mariella, additional, Giai, Valentina, additional, Rocci, Alberto, additional, Monitillo, Luigia, additional, Drandi, Daniela, additional, Ferrero, Simone, additional, Isaia, Gianluca, additional, Bernocco, Elisa, additional, Boi, Michela, additional, Lunghi, Monia, additional, Abruzzese, Elisabetta, additional, Pini, Massimo, additional, Radaelli, Franca, additional, Pregno, Patrizia, additional, Passera, Roberto, additional, Gaidano, Gianluca, additional, Boccadoro, Mario, additional, Carlo-Stella, Carmelo, additional, and Ladetto, Marco, additional

Published
2009
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38. Characteristics of the Immunoglobulin Heavy Chain (IgH) Rearrangement in Multiple Myeloma (MM): An Analysis On 308 Cases.

Author

Ferrero, Simone, primary, Capello, Daniela, additional, Svaldi, Mirija, additional, Boi, Michela, additional, Drandi, Daniela, additional, Rossi, Davide, additional, Pagliano, Gloria, additional, Monitillo, Luigia, additional, Bodoni, Chiara Lobetti, additional, Genuardi, Elisa, additional, Critelli, Rossana, additional, Bussano, Serena, additional, Barbero, Daniela, additional, Mantoan, Barbara, additional, Bernocco, Elisa, additional, Palumbo, Antonio, additional, Boccadoro, Mario, additional, Gaidano, Gianluca, additional, Cortelazzo, Sergio, additional, and Ladetto, Marco, additional

Published
2009
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39. Correlation Between Clinical Outcome and Disease Kinetics by Quantitative PCR in Myeloma Patients Following Post-Transplant Consolidation with Bortezomib, Thalidomide and Dexamethasone.

Author

Ladetto, Marco, primary, Pagliano, Gloria, additional, Ferrero, Simone, additional, Cavallo, Federica, additional, Drandi, Daniela, additional, Boi, Michela, additional, Santo, Loredana, additional, Crippa, Claudia, additional, De Rosa, Luca, additional, Pregno, Patrizia, additional, Grasso, Mariella, additional, Liberati, Anna Marina, additional, Caravita, Tommaso, additional, Pisani, Francesco, additional, Guglielmelli, Tommasina, additional, Callea, Vincenzo, additional, Rossini, Fausto, additional, Musto, Pellegrino, additional, Cangialosi, Clotilde, additional, Rocci, Alberto, additional, Passera, Roberto, additional, Boccadoro, Mario, additional, and Palumbo, Antonio, additional

Published
2009
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40. Telomere Length Is An Independent Predictor of Survival, Treatment Requirement and Richter’s Syndrome Transformation in Chronic Lymphocytic Leukemia.

Author

Rossi, Davide, primary, Bodoni, Chiara Lobetti, primary, Genuardi, Elisa, primary, Monitillo, Luigia, primary, Drandi, Daniela, primary, Deambrogi, Clara, primary, Cerri, Michaela, primary, Ricca, Irene, primary, Rocci, Alberto, primary, Ferrero, Simone, primary, Bernocco, Elisa, primary, Capello, Daniela, primary, De Paoli, Lorenzo, primary, Bergui, Luciana, primary, Boi, Michela, primary, Omedè, Paola, primary, Massaia, Massimo, primary, Tarella, Corrado, primary, Passera, Roberto, primary, Boccadoro, Mario, primary, Gaidano, Gianluca, primary, and Ladetto, Marco, primary

Published
2008
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41. Major Shrinking of Residual Tumor Cell Burden and Achievement of Molecular Remissions in Myeloma Patients Undergoing Post-Trasplant Consolidation with Bortezomib, Thalidomide and Dexamethasone: A Qualitative and Quantitative PCR Study

Author

Ladetto, Marco, primary, Pagliano, Gloria, additional, Ferrero, Simone, additional, Cavallo, Federica, additional, Drandi, Daniela, additional, Boi, Michela, additional, Santo, Loredana, additional, Pregno, Patrizia, additional, Grasso, Mariella, additional, Liberati, Anna Marina, additional, Caravita, Tommaso, additional, Pisani, Francesco, additional, Crippa, Claudia, additional, Callea, Vincenzo, additional, Falcone, Antonietta, additional, Morandi, Sergio, additional, Boccadoro, Mario, additional, and Palumbo, Antonio, additional

Published
2008
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42. PRDM1/BLIMP1: a tumor suppressor gene in B and T cell lymphomas.

Author

Boi, Michela, Zucca, Emanuele, Inghirami, Giorgio, and Bertoni, Francesco

Subjects
*TUMOR suppressor genes, *T cells, *B cells, *LYMPHOID tissue, *CELL differentiation, *KILLER cells
Abstract

The gene encoding the human BLIMP1, prdm1, is located on chromosome 6q21, a locus frequently deleted in lymphoid tumors. BLIMP1 is able to silence its target genes in a context-dependent manner through different mechanisms. BLIMP1 is expressed in both B and T cells, in which it plays important functions. In B cells, BLIMP1 acts as the master regulator of plasma cell differentiation, repressed by BCL6 and repressing both BCL6 and PAX5. In T cells, BLIMP1 is a critical factor for most terminal effector cell differentiation in both CD4+ and CD8+ T cells. BLIMP1 is frequently inactivated in a variety of lymphomas, including diffuse large B cell lymphomas, Natural Killer cell lymphoma and anaplastic large T cell lymphoma. In this review, we will summarize the role of BLIMP1 in normal cells, focusing on lymphoid cells, and on its function as tumor suppressor gene in lymphomas. [ABSTRACT FROM AUTHOR]

Published
2015
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43. Immunoglobulin (Ig) Repertoire in Multiple Myeloma: High Frequency of Recurrent Aminoacid Substitutions in the FR2 and CDR2.

Author

Ladetto, Marco, primary, Drandi, Daniela, additional, Santo, Loredana, additional, Mantoan, Barbara, additional, Boi, Michela, additional, Dell’Aquila, Maria, additional, Monitillo, Luigia, additional, Bodoni, Chiara Lobetti, additional, Palumbo, Antonio, additional, Astolfi, Monica, additional, and Boccadoro, Mario, additional

Published
2006
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44. The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs

Author

Emanuele Zucca, Maurilio Ponzoni, Georg Stussi, Andrea Rinaldi, Eugenio Gaudio, Maria E. Riveiro, Ivo Kwee, Afua Adjeiwaa Mensah, Giorgio Inghirami, Luciano Cascione, Paola Bonetti, Monica Testoni, Esteban Cvitkovic, Patrice Herait, Francesco Bertoni, Chiara Tarantelli, Elena Bernasconi, Michela Boi, Anastasios Stathis, Boi, Michela, Gaudio, Eugenio, Bonetti, Paola, Kwee, Ivo, Bernasconi, Elena, Tarantelli, Chiara, Rinaldi, Andrea, Testoni, Monica, Cascione, Luciano, Ponzoni, Maurilio, Mensah, Afua Adjeiwaa, Stathis, Anastasio, Stussi, Georg, Riveiro, María Eugenia, Herait, Patrice, Inghirami, Giorgio, Cvitkovic, Esteban, Zucca, Emanuele, and Bertoni, Francesco

Subjects
Cancer Research, Chromatin Immunoprecipitation, Lymphoma, B-Cell, Blotting, Western, Antineoplastic Agents, Apoptosis, Mice, SCID, Biology, Real-Time Polymerase Chain Reaction, Mice, In vivo, Mice, Inbred NOD, Cell Line, Tumor, medicine, Animals, Humans, Epigenetics, PI3K/AKT/mTOR pathway, B cell, Cell Proliferation, Cancer, Nuclear Proteins, Drug Synergism, Epigenome, medicine.disease, Immunohistochemistry, Xenograft Model Antitumor Assays, Bromodomain, medicine.anatomical_structure, Oncology, Immunology, Cancer cell, Cancer research, Acetanilides, Transcriptome, Heterocyclic Compounds, 3-Ring
Abstract

Purpose: In cancer cells, the epigenome is often deregulated, and inhibition of the bromodomain and extra-terminal (BET) family of bromodomain-containing proteins is a novel epigenetic therapeutic approach. Preliminary results of an ongoing phase I trial have reported promising activity and tolerability with the new BET bromodomain inhibitor OTX015. Experimental Design: We assessed the preclinical activity of OTX015 as single agent and in combination in mature B-cell lymphoma models and performed in vitro and in vivo experiments to identify the mechanism of action and the genetic features associated with sensitivity to the compound. Results: OTX015 showed antiproliferative activity in a large panel of cell lines derived from mature B-cell lymphoid tumors with median IC50 of 240 nmol/L, without significant differences among the different histotypes. In vitro and in vivo experiments showed that OTX015 targeted NFKB/TLR/JAK/STAT signaling pathways, MYC- and E2F1-regulated genes, cell-cycle regulation, and chromatin structure. OTX015 presented in vitro synergism with several anticancer agents, especially with mTOR and BTK inhibitors. Gene expression signatures associated with different degrees of sensitivity to OTX015 were identified. Although OTX015 was mostly cytostatic, the compound induced apoptosis in a genetically defined subgroup of cells, derived from activated B-cell–like diffuse large B-cell lymphoma, bearing wtTP53, mutations in MYD88, and CD79B or CARD11. Conclusions: Together with the data coming from the ongoing phase I study, the in vitro and in vivo data presented here provide the basis for further clinical investigation of OTX015 as single agent and in combination therapies. Clin Cancer Res; 21(7); 1628–38. ©2015 AACR.

Published
2015

45. Convergent Mutations and Kinase Fusions Lead to Oncogenic STAT3 Activation in Anaplastic Large Cell Lymphoma

Author

Lorenzo Cerroni, Laurence Mevellec, Andreas Rosenwald, Giorgio Inghirami, Luigi Barbarossa, Elena Lasorsa, Enrico Tiacci, Miguel A. Piris, Francesco Bertoni, Davide Rossi, Elisabetta Ercole, Nicoletta Chiesa, Filomena Di Giacomo, Domenico Novero, Maria Todaro, Alberto Zamò, Jorge Vialard, Ramona Crescenzo, Alexander Tzankov, Andrea Rinaldi, Lukas Kenner, Leonard D. Shultz, Francesco Abate, Thomas Tousseyn, Raul Rabadan, Javeed Iqbal, Dennis D. Weisenburger, Brunangelo Falini, Carmela Ciardullo, Elisa Ficarra, Wing C. Chan, Gianluca Gaidano, Elisa Spaccarotella, Andrea Acquaviva, Roberto Piva, Stefano Pileri, Fabrizio Tabbò, Marcello Gaudiano, Michela Boi, Marco Paulli, Maurilio Ponzoni, Crescenzo, Ramona, Abate, Francesco, Lasorsa, Elena, Tabbo', Fabrizio, Gaudiano, Marcello, Chiesa, Nicoletta, Di Giacomo, Filomena, Spaccarotella, Elisa, Barbarossa, Luigi, Ercole, Elisabetta, Todaro, Maria, Boi, Michela, Acquaviva, Andrea, Ficarra, Elisa, Novero, Domenico, Rinaldi, Andrea, Tousseyn, Thoma, Rosenwald, Andrea, Kenner, Luka, Cerroni, Lorenzo, Tzankov, Alexander, Ponzoni, Maurilio, Paulli, Marco, Weisenburger, Denni, Chan, Wing C, Iqbal, Javeed, Piris, Miguel A, Zamo', Alberto, Ciardullo, Carmela, Rossi, Davide, Gaidano, Gianluca, Pileri, Stefano, Tiacci, Enrico, Falini, Brunangelo, Shultz, Leonard D, Mevellec, Laurence, Vialard, Jorge E, Piva, Roberto, Bertoni, Francesco, Rabadan, Raul, Inghirami, Giorgio, Ramona Crescenzo, Francesco Abate, Elena Lasorsa, Fabrizio Tabbo’, Marcello Gaudiano, Nicoletta Chiesa, Filomena Di Giacomo, Elisa Spaccarotella, Luigi Barbarossa, Elisabetta Ercole, Maria Todaro, Michela Boi, ACQUAVIVA, ANDREA, FICARRA, ELISA, Domenico Novero, Andrea Rinaldi, Thomas Tousseyn, Andreas Rosenwald, Lukas Kenner, Lorenzo Cerroni, Alexander Tzankov, Maurilio Ponzoni, Marco Paulli, Dennis Weisenburger, Wing C. Chan, Javeed Iqbal, Miguel A. Piri, Alberto Zamo’, Carmela Ciardullo, Davide Rossi, Gianluca Gaidano, Stefano Pileri, Enrico Tiacci, Brunangelo Falini, Leonard D. Shultz, Laurence Mevellec, Jorge E. Vialard, Roberto Piva, Francesco Bertoni, Raul Rabadan, and Giorgio Inghirami

Subjects
Cancer Research, Lymphoma, Somatic cell, massive sequencing, Activating Transcription Factor 3, Animals, Cell Line, Tumor, HEK293 Cells, Humans, Janus Kinase 1, Lymphoma, Large-Cell, Anaplastic, Mice, Mutant Chimeric Proteins, NF-kappa B, Phosphorylation, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, STAT3 Transcription Factor, Signal Transduction, TYK2 Kinase, Gene Expression Regulation, Neoplastic, Cell Biology, Oncology, Medicine (all), Anaplastic Large Cell Lymphoma, JAK/STAT3 pathway, Oncogenic STAT3 Activation, gene fusions, 0302 clinical medicine, hemic and lymphatic diseases, RNA-Seq data, anaplastic large cell lymphoma (ALCL), driver genetic alterations, somatic point mutations, copy number alterations, Anaplastic, Anaplastic lymphoma kinase, Anaplastic large-cell lymphoma, 0303 health sciences, Tumor, Janus kinase 1, Kinase, Large-Cell, 3. Good health, driver genetic alteration, somatic point mutation, Tyrosine kinase 2, 030220 oncology & carcinogenesis, Tyrosine kinase, Biology, Article, Cell Line, 03 medical and health sciences, ROS1, medicine, 030304 developmental biology, Stat3 activation, Neoplastic, Point mutation, gene fusion, medicine.disease, Molecular biology, Gene Expression Regulation, Cancer cell, Cancer research
Abstract

JAK/STAT3 signaling pathway is often deregulated in hematopoietic disorders including peripheral T-cell lymphoma. We describe two novel mechanisms leading to the constitutive activation of STAT3 in ALK- ALCL. Oncogenic JAK1 or STAT3 mutations are associated to hyperactive pSTAT3 that regulated canonical STAT3 and ATF3 genes. Moreover, synergizing JAK1 and STAT3 mutants sustain the neoplastic growth, which can be efficiently controlled in vitro and in an ALCL patient derived tumorgraft model by JAK1/2 inhibitors. We have discovered that novel chimera, displaying concomitant transcriptional and kinase activities, are power oncogenes capable to sustain via STAT3 the ALCL phenotype and can be uniquely neutralized by a novel ROS1 inhibitor. The pharmacological inhibition of JAK/STAT3 represents a novel strategy for the treatment of molecular stratified ALCL.

Published
2015

46. Chemometrics for the direct analysis of solid samples by spectroscopic and chromatographic techniques

Author

Melucci, D., Cocchi, M., Corvucci, F., Boi, M., Tositti, L., Laurentiis, F., Alessandro Zappi, Locatelli, C., Locatelli, M., Aderval S. Luna, Melucci, Dora, Cocchi, Marina, Corvucci, Francesca, Boi, Michela, Tositti, Laura, Laurentiis, Francesco de, Zappi, Alessandro, Locatelli, Clinio, and Locatelli, Marcello

Subjects
chemometrics, LASSO, SPLS, elastic-net, Py-GC-MS, Raman, ATR
Abstract

The direct chemical analysis allows investigating samples without altering them, keeping the sample available for further analysis. For the qualitative investigation, analytical procedures like gas-chromatography, Raman microscopy, and Infra Red spectroscopy are available; however, the univariate approach is not exhaustive in the case of very complex matrices. The quantitative approach is still an open issue, due to the strong matrix effect hindering the creation of univariate calibration methods in interpolation mode. The multivariate analysis may be the solution. Three-way Principal Components Analysis (PCA) allows for comprehension of variables influencing classification. The Partial Least Squares regression (PLS) combined with Discriminant Analysis (DA) allows classifying. Multivariate standard addition calibration based on PLS coupled with Net Analyte Signal (NAS) calculation allows bypassing the matrix effect in quantitative analysis. This Chapter is focused on the issues mentioned above. Three sections will be presented: SECTION 1: three-way PCA is applied to the discrimination among bacterial species in samples analyzed as such by pyrolysis gas chromatography-mass spectrometry. Applications to timely analysis of pathogenic microbes are foreseen. SECTION 2: PLS-DA is applied to Raman spectra to discriminate adulterated beeswaxes from natural ones. This procedure may be implemented to prevent possible adulteration of bees’ products. SECTION 3: PLS-NAS is applied to ATR spectra to quantify biogenic silica in marine sediments. The new method allows to accurately study the time evolution of primary productivity in the Antarctic basins.

47. Therapeutic efficacy of the bromodomain inhibitor OTX015/MK-8628 in ALK-positive anaplastic large cell lymphoma: an alternative modality to overcome resistant phenotypes.

Author

Boi M, Todaro M, Vurchio V, Yang SN, Moon J, Kwee I, Rinaldi A, Pan H, Crescenzo R, Cheng M, Cerchietti L, Elemento O, Riveiro ME, Cvitkovic E, Bertoni F, and Inghirami G

Subjects
Anaplastic Lymphoma Kinase, Antineoplastic Combined Chemotherapy Protocols pharmacology, Cell Cycle Checkpoints drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Synergism, Gene Expression Profiling methods, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Humans, Inhibitory Concentration 50, Lymphoma, Large-Cell, Anaplastic genetics, Lymphoma, Large-Cell, Anaplastic pathology, Phenotype, Signal Transduction drug effects, Time Factors, Transcriptome, Acetanilides pharmacology, Antineoplastic Agents pharmacology, Biomarkers, Tumor genetics, Drug Resistance, Neoplasm drug effects, Heterocyclic Compounds, 3-Ring pharmacology, Lymphoma, Large-Cell, Anaplastic drug therapy, Receptor Protein-Tyrosine Kinases genetics
Abstract

Anaplastic large cell lymphomas (ALCL) represent a peripheral T-cell lymphoma subgroup, stratified based on the presence or absence of anaplastic lymphoma kinase (ALK) chimeras. Although ALK-positive ALCLs have a more favorable outcome than ALK-negative ALCL, refractory and/or relapsed forms are common and novel treatments are needed. Here we investigated the therapeutic potential of a novel bromodomain inhibitor, OTX015/MK-8628 in ALK-positive ALCLs.The effects of OTX015 on a panel of ALK+ ALCL cell lines was evaluated in terms of proliferation, cell cycle and downstream signaling, including gene expression profiling analyses. Synergy was tested with combination targeted therapies.Bromodomain inhibition with OTX015 led primarily to ALCL cell cycle arrest in a dose-dependent manner, along with downregulation of MYC and its downstream regulated genes. MYC overexpression did not compensate this OTX015-mediated phenotype. Transcriptomic analysis of OTX015-treated ALCL cells identified a gene signature common to various hematologic malignancies treated with bromodomain inhibitors, notably large cell lymphoma. OTX015-modulated genes included transcription factors (E2F2, NFKBIZ, FOS, JUNB, ID1, HOXA5 and HOXC6), members of multiple signaling pathways (ITK, PRKCH, and MKNK2), and histones (clusters 1-3). Combination of OTX015 with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib led to cell cycle arrest then cell death, and combination with suboptimal doses of the ALK inhibitor CEP28122 caused cell cycle arrest. When OTX015 was associated with GANT61, a selective GLI1/2 inhibitor, C1156Y-resistant ALK ALCL growth was impaired.These findings support OTX015 clinical trials in refractory ALCL in combination with inhibitors of interleukin-2-inducible kinase or SHH/GLI1.

Published
2016
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48. Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes.

Author

Ferrero S, Capello D, Svaldi M, Boi M, Gatti D, Drandi D, Rossi D, Barbiero S, Mantoan B, Mantella E, Zanni M, Ghione P, Larocca A, Passera R, Bertoni F, Gattei V, Forconi F, Laurenti L, Del Poeta G, Marasca R, Cortelazzo S, Gaidano G, Palumbo A, Boccadoro M, and Ladetto M

Subjects
B-Lymphocytes immunology, B-Lymphocytes pathology, Complementarity Determining Regions chemistry, Complementarity Determining Regions immunology, Data Mining, Databases, Nucleic Acid, Humans, Multigene Family immunology, Multiple Myeloma immunology, Myeloma Proteins chemistry, Myeloma Proteins immunology, Sequence Analysis, DNA, Somatic Hypermutation, Immunoglobulin immunology, Complementarity Determining Regions genetics, Genes, Immunoglobulin Heavy Chain immunology, Multiple Myeloma genetics, Myeloma Proteins genetics
Abstract

Background: Characterization of the immunoglobulin gene repertoire has improved our understanding of the immunopathogenesis of lymphoid tumors. Early B-lymphocyte precursors of multiple myeloma are known to exist and might be susceptible to antigenic drive., Design and Methods: To verify this hypothesis, we collected a database of 345 fully readable multiple myeloma immunoglobulin sequences. We characterized the immunoglobulin repertoire, analyzed the somatic hypermutation load, and investigated for stereotyped receptor clusters., Results: Compared to the normal immunoglobulin repertoire, multiple myeloma displayed only modest differences involving only a few genes, showing that the myeloma immunoglobulin repertoire is the least skewed among mature B-cell tumors. Median somatic hypermutation load was 7.8%; median length of complementarity determining-region 3 was 15.5 amino acids. Clustering analysis showed the absence of myeloma specific clusters and no similarity with published chronic lymphocytic leukemia or lymphoma subsets., Conclusions: Analysis of multiple myeloma immunoglobulin repertoire does not support a pathogenetic role for antigen selection in this tumor.

Published
2012
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