Annals of Hematology

, Volume 91, Issue 12, pp 1887–1895 | Cite as

Simultaneous analysis of the expression of 14 genes with individual prognostic value in myelodysplastic syndrome patients at diagnosis: WT1 detection in peripheral blood adversely affects survival

  • Carlos Santamaría
  • Fernando Ramos
  • Noemi Puig
  • Eva Barragán
  • Raquel de Paz
  • Carme Pedro
  • Andrés Insunza
  • Mar Tormo
  • Consuelo del Cañizo
  • María Diez-Campelo
  • Blanca Xicoy
  • Eduardo Salido
  • Javier Sánchez del Real
  • Montserrat Hernández
  • Carmen Chillón
  • Guillermo F. Sanz
  • Ramón García-Sanz
  • Jesús F. San Miguel
  • Marcos González
Original Article

Abstract

Several studies have evaluated the prognostic value of the individual expression of certain genes in patients with myelodysplastic syndromes (MDS). However, none of them includes their simultaneous analysis by quantitative polymerase chain reaction (PCR). We evaluated relative expression levels of 14 molecular markers in 193 peripheral blood samples from untreated MDS patients using real-time PCR. Detectable WT1 expression levels, low TET2, and low IER3 gene expression were the only markers showing in univariate analysis a poor prognostic value for all treatment-free (TFS), progression-free (PFS), and overall survival (OS). In multivariate analysis, molecular parameters associated with a shorter TFS were: WT1 detection (p = 0.014), low TET2 (p = 0.002), and low IER3 expression (p = 0.025). WT1 detection (p = 0.006) and low TET2 (p = 0.006) expression were associated with a shorter PFS when multivariate analysis was carried out by including only molecular markers. Molecular values with an independent value in OS were: WT1 detection (p = 0.003), high EVI1 expression (p = 0.001), and undetectatable p15-CDKN2B (p = 0.037). WT1 expressers were associated with adverse clinical–biological features, high IPSS and WPSS scoring, and unfavorable molecular expression profile. In summary, detectable WT1 expression levels, and low TET2 and low IER3 expression in peripheral blood showed a strong association with adverse prognosis in MDS patients at diagnosis. However, WT1 was the only molecular marker displaying an independent prognostic value in both OS and TFS.

Keywords

Myelodysplastic syndrome WT1 Molecular prognosis Real-time PCR 

Notes

Acknowledgments

The Spanish MDS Group (GESMD), provided samples and clinical information from patients participating in the INBIOMED HEMA-001/2006 project (sponsored by Celgene S.L., Madrid). This work has been partially supported by the grants PI061351 and 00/0023-00 from the Spanish “Fondo de Investigaciones Sanitarias de la Seguridad Social”, 89/A/06 from the “Gerencia Regional de Salud, Junta Castilla y León”, and CIC, IBMCC (USAL-CSIC), Spain.

Conflicts of interest

All the authors have no conflict of interest to report.

Supplementary material

277_2012_1538_MOESM1_ESM.doc (46 kb)
Supplementary Table 1Clinical and biological characteristics of MDS patients at diagnosis according to WT1 expression levels (DOC 46 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Carlos Santamaría
    • 1
    • 12
  • Fernando Ramos
    • 2
    • 11
  • Noemi Puig
    • 1
  • Eva Barragán
    • 3
  • Raquel de Paz
    • 4
  • Carme Pedro
    • 5
  • Andrés Insunza
    • 6
  • Mar Tormo
    • 7
  • Consuelo del Cañizo
    • 1
    • 12
  • María Diez-Campelo
    • 1
  • Blanca Xicoy
    • 8
  • Eduardo Salido
    • 9
  • Javier Sánchez del Real
    • 2
  • Montserrat Hernández
    • 1
  • Carmen Chillón
    • 1
  • Guillermo F. Sanz
    • 10
  • Ramón García-Sanz
    • 1
    • 12
  • Jesús F. San Miguel
    • 1
    • 12
  • Marcos González
    • 1
    • 12
  1. 1.Servicio de HematologíaHospital Universitario de SalamancaSalamancaSpain
  2. 2.Servicio de Hematología, Hospital de LeónLeónSpain
  3. 3.Laboratorio de Biología MolecularHospital Universitario La FeValenciaSpain
  4. 4.Servicio de HematologíaH. Universitario La PazMadridSpain
  5. 5.Servicio de Hematología, Hospital del MarBarcelonaSpain
  6. 6.Servicio de HematologíaHospital Universitario Marqués de ValdecillaSantanderSpain
  7. 7.Servicio de Hematología y OncologíaHospital Clínico UniversitarioValenciaSpain
  8. 8.Servicio de HematologíaHospital Universitario Germans Trias i PujolBadalonaSpain
  9. 9.Servicio de HematologíaHospital Universitario Virgen de la ArrixacaMurciaSpain
  10. 10.Servicio de HematologíaHospital Universitario La FeValenciaSpain
  11. 11.Instituto de Biomedicina (IBIOMED)Universidad de LeónLeónSpain
  12. 12.Centro de Investigación del Cáncer-IBMCC (USAL-CSIC)SalamancaSpain

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