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

Esther Natalie Oliva, Maria Cuzzola, Maria Antonietta Aloe Spiriti, Antonella Poloni, Carmelo Laganà, Carmela Rigolino, Fortunato Morabito, Sara Galimberti, Riccardo Ghio, Agostino Cortelezzi, Giuseppe Alberto Palumbo, Grazia Sanpaolo, Carlo Finelli, Alessandra Ricco, Antonio Volpe, Filippo Rodà, Massimo Breccia, Giuliana Alimena, Francesco Nobile, Roberto Latagliata

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalAnnals of Hematology
Volume92
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • del5q-
  • Lenalidomide
  • MDS
  • miRNAs
  • RPS-14

ASJC Scopus subject areas

  • Hematology

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    Oliva, E. N., Cuzzola, M., Aloe Spiriti, M. A., Poloni, A., Laganà, C., Rigolino, C., Morabito, F., Galimberti, S., Ghio, R., Cortelezzi, A., Palumbo, G. A., Sanpaolo, G., Finelli, C., Ricco, A., Volpe, A., Rodà, F., Breccia, M., Alimena, G., Nobile, F., & Latagliata, R. (2013). Biological activity of lenalidomide in myelodysplastic syndromes with del5q: Results of gene expression profiling from a multicenter phase II study. Annals of Hematology, 92(1), 25-32. https://doi.org/10.1007/s00277-012-1569-0