Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome

Wolf C. Prall, Akos Czibere, Franck Grall, Dimitrios Spentzos, Ulrich Steidl, Aristoteles Achilles Nikolaus Giagounidis, Andrea Kuendgen, Hasan Otu, Astrid Rong, Towia A. Libermann, Ulrich Germing, Norbert Gattermann, Rainer Haas, Manuel Aivado

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

One feature of the molecular pathology of myelodysplastic syndromes (MDS) is aberrant gene expression. Such aberrations may be related to patient survival, and may indicate to novel diagnostic and therapeutic targets. Therefore, we aimed at identifying aberrant gene expression that is associated with MDS and patient survival. Bone marrow-derived CD34+ hematopoietic progenitor cells from six healthy persons and 16 patients with MDS were analyzed on cDNA macroarrays comprising 1,185 genes. Thereafter, our patients were followed-up for 54 months. We found differential expression of genes that were hitherto unrecognized in the context of MDS. Differential expression of 10 genes was confirmed by quantitative real-time RT-PCR. Hierarchical cluster analysis facilitated the separation of CD34+ cells of normal donors from patients with MDS. More importantly, it also distinguished MDS-patients with short and long survival. Scrutinizing our cDNA macroarray data for genes that are associated with short survival, we found, among others, increased expression of six different genes that encode the proteasome subunits. On the other hand, the most differentially down-regulated gene was IEX-1, which encodes an anti-apoptotic protein. We confirmed its decreased expression on RNA and protein level in an independent validation set of patient samples. The presented data broadens our notion about the molecular pathology of MDS and may lend itself to better identify patients with short survival. Furthermore, our findings may help to define new molecular targets for drug development and therapeutic approaches for patients with poor prognosis.

Original languageEnglish (US)
Pages (from-to)173-187
Number of pages15
JournalInternational Journal of Hematology
Volume89
Issue number2
DOIs
StatePublished - Mar 2009

Keywords

  • Gene expression
  • IEX-1
  • MDS
  • Survival
  • cDNA array

ASJC Scopus subject areas

  • Hematology

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    Prall, W. C., Czibere, A., Grall, F., Spentzos, D., Steidl, U., Giagounidis, A. A. N., Kuendgen, A., Otu, H., Rong, A., Libermann, T. A., Germing, U., Gattermann, N., Haas, R., & Aivado, M. (2009). Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome. International Journal of Hematology, 89(2), 173-187. https://doi.org/10.1007/s12185-008-0242-9