International Journal of Hematology

, Volume 104, Issue 5, pp 566–573 | Cite as

Up-regulation of ribosomal genes is associated with a poor response to azacitidine in myelodysplasia and related neoplasms

  • M. Monika Belickova
  • Michaela Dostalova Merkerova
  • Hana Votavova
  • Jan Valka
  • Jitka Vesela
  • Barbora Pejsova
  • Hana Hajkova
  • Jiri Klema
  • Jaroslav Cermak
  • Anna Jonasova
Original Article


Azacitidine (AZA) is a hypomethylating drug used to treat disorders associated with myelodysplasia and related neoplasms. Approximately 50 % of patients do not respond to AZA and have very poor outcomes. There is thus great interest in identifying predictive biomarkers for AZA responsiveness. We searched for specific genes whose expression level was associated with response status. Using microarrays, we analyzed gene expression patterns in bone marrow CD34+ cells in serial samples from 32 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes before and during the AZA therapy. At baseline, a comparison of the responders and non-responders showed 52 differentially expressed genes (P < 0.01). Functional annotation of the deregulated genes revealed categories primarily related to ribosomes and pathways associated with proliferation. The expression level of RPL28 correlated with overall survival. We identified altered expression in 167 genes in responders, 26 genes in non-responders with stable disease, and 13 genes in non-responders with disease progression using paired t test of expression levels in patients before and during treatment. Our data indicate that AZA treatment failure is associated with the up-regulation of ribosomal genes/pathways that are likely related to intensive proteosynthesis in proliferative/neoplastic cells of non-responders.


Myelodysplastic syndromes Ribosomal genes Azacitidine Gene expression profiling 



This work has been supported by the Internal Grant Agency of the Ministry of Health of the Czech Republic NT/14377.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

Supplementary material

12185_2016_2058_MOESM1_ESM.docx (568 kb)
Supplementary material 1 (DOCX 567 kb)


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Copyright information

© The Japanese Society of Hematology 2016

Authors and Affiliations

  • M. Monika Belickova
    • 1
  • Michaela Dostalova Merkerova
    • 1
  • Hana Votavova
    • 1
  • Jan Valka
    • 1
  • Jitka Vesela
    • 1
  • Barbora Pejsova
    • 1
  • Hana Hajkova
    • 1
  • Jiri Klema
    • 2
  • Jaroslav Cermak
    • 1
  • Anna Jonasova
    • 3
  1. 1.Department of GenomicsInstitute of Hematology and Blood TransfusionPrague 2Czech Republic
  2. 2.Department of Computer ScienceFaculty of Electrical Engineering, Czech Technical UniversityPragueCzech Republic
  3. 3.1st Department of MedicineGeneral University Hospital PraguePragueCzech Republic

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