Biological activity of lenalidomide in myelodysplastic syndromes with del5q: results of gene expression profiling from a multicenter phase II study

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• 作者：Esther Natalie Oliva (1)
  Maria Cuzzola (2)
  Maria Antonietta Aloe Spiriti (3)
  Antonella Poloni (4)
  Carmelo Laganà (5)
  Carmela Rigolino (2)
  Fortunato Morabito (6)
  Sara Galimberti (7)
  Riccardo Ghio (8)
  Agostino Cortelezzi (9)
  Giuseppe Alberto Palumbo (10)
  Grazia Sanpaolo (11)
  Carlo Finelli (12)
  Alessandra Ricco (13)
  Antonio Volpe (14)
  Filippo Rodà (1)
  Massimo Breccia (15)
  Giuliana Alimena (15)
  Francesco Nobile (1)
  Roberto Latagliata (15)
  
• 关键词：del5q?/li> Lenalidomide ; MDS ; miRNAs ; RPS ; 14
• 刊名：Annals of Hematology
• 出版年：2013
• 出版时间：January 2013
• 年：2013
• 卷：92
• 期：1
• 页码：25-32
• 全文大小：217KB
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• 作者单位：Esther Natalie Oliva (1)
  Maria Cuzzola (2)
  Maria Antonietta Aloe Spiriti (3)
  Antonella Poloni (4)
  Carmelo Laganà (5)
  Carmela Rigolino (2)
  Fortunato Morabito (6)
  Sara Galimberti (7)
  Riccardo Ghio (8)
  Agostino Cortelezzi (9)
  Giuseppe Alberto Palumbo (10)
  Grazia Sanpaolo (11)
  Carlo Finelli (12)
  Alessandra Ricco (13)
  Antonio Volpe (14)
  Filippo Rodà (1)
  Massimo Breccia (15)
  Giuliana Alimena (15)
  Francesco Nobile (1)
  Roberto Latagliata (15)
  
  1. Haematology Unit, Azienda Ospedaliera “Bianchi-Melacrino-Morelli- Via Melacrino, 89100, Reggio, Calabria, Italy
  2. Bone Marrow Transplantation Unit, Azienda Ospedaliera “Bianchi-Melacrino-Morelli- Reggio, Calabria, Italy
  3. Haematology Department, A.O. Sant’Andrea, Rome, Italy
  4. Haematology Unit, Università Politecnica delle Marche, Ancona, Italy
  5. Medical Cytogenetics, Azienda Ospedaliera “Bianchi-Melacrino-Morelli- Reggio, Calabria, Italy
  6. Haematology Unit, Azienda Ospedaliera di Cosenza, Cosenza, Italy
  7. Department of Oncology, Transplants and Advanced Technologies, St. Chiara Hospital, University of Pisa, Pisa, Italy
  8. Haematology Unit, San Martino Hospital, Genova, Italy
  9. Fondazione IRCCS Ca-Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
  10. Haematology Unit, Azienda Ospedaliero-Universitaria “Policlinico-Vittorio Emanuele- Catania, Italy
  11. Haematology Division, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
  12. Department of Haematology, University of Bologna, Bologna, Italy
  13. Department of Haematology, University of Bari, Bari, Italy
  14. Haematology Division, San Giuseppe Moscati Hospital, Avellino, Italy
  15. Department of Cellular Biotechnology and Haematology, Sapienza University, Sapienza, Rome, Italy
  
• ISSN：1432-0584

文摘

In vitro studies suggest that haploinsufficiency is involved in the pathogenesis of myelodysplastic syndromes (MDS). In patients with del5q cytogenetic abnormality, RPS-14 and microRNAs (miRNAs) play a major role. In a multicenter phase II single-arm trial with lenalidomide in anemic primary del5q MDS patients with low- or int-1 risk IPSS, biological changes from baseline were investigated. Gene expression profiling of selected genes was performed (TaqMan? Low Density Array Fluidic card, Applied Biosystems PRISM? 7900HT) and normalized against the expression of the 18S housekeeping gene from a pool of healthy subjects. Thirty-two patients were evaluated at baseline and after 3 and 6?months of treatment. RPS-14, miR-145, and miR-146 were downregulated at baseline and significantly increased during treatment. Nuclear factor kappa B, IL-6, interferon regulatory factor-1, IFNγ-R2, IL-2, and many genes in the apoptotic pathways (TNF, IL-1B, and IL-10) were upregulated at baseline and significantly downregulated during lenalidomide treatment, while forkhead box P3, FAS, IFNγ, IL-12A, and IL-12B were downregulated at baseline and progressively upregulated during treatment. The crucial role of aberrant immunological pathways and haploinsufficiency in the pathogenesis of del5q MDS is confirmed in the present patient setting. Our results indicate that lenalidomide may act through defined immunological pathways in this condition.