Annals of Hematology

, Volume 92, Issue 1, pp 25–32

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
Original Article

DOI: 10.1007/s00277-012-1569-0

Cite this article as:
Oliva, E.N., Cuzzola, M., Aloe Spiriti, M.A. et al. Ann Hematol (2013) 92: 25. doi:10.1007/s00277-012-1569-0

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.

Keywords

del5q− Lenalidomide MDS miRNAs RPS-14 

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • 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. 1.Haematology UnitAzienda Ospedaliera “Bianchi-Melacrino-Morelli”ReggioItaly
  2. 2.Bone Marrow Transplantation UnitAzienda Ospedaliera “Bianchi-Melacrino-Morelli”ReggioItaly
  3. 3.Haematology DepartmentA.O. Sant’AndreaRomeItaly
  4. 4.Haematology UnitUniversità Politecnica delle MarcheAnconaItaly
  5. 5.Medical CytogeneticsAzienda Ospedaliera “Bianchi-Melacrino-Morelli”ReggioItaly
  6. 6.Haematology UnitAzienda Ospedaliera di CosenzaCosenzaItaly
  7. 7.Department of Oncology, Transplants and Advanced Technologies, St. Chiara HospitalUniversity of PisaPisaItaly
  8. 8.Haematology UnitSan Martino HospitalGenovaItaly
  9. 9.Fondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoUniversity of MilanMilanItaly
  10. 10.Haematology UnitAzienda Ospedaliero-Universitaria “Policlinico-Vittorio Emanuele”CataniaItaly
  11. 11.Haematology DivisionCasa Sollievo della Sofferenza HospitalSan Giovanni RotondoItaly
  12. 12.Department of HaematologyUniversity of BolognaBolognaItaly
  13. 13.Department of HaematologyUniversity of BariBariItaly
  14. 14.Haematology DivisionSan Giuseppe Moscati HospitalAvellinoItaly
  15. 15.Department of Cellular Biotechnology and HaematologySapienza UniversityRomeItaly

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