Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells

A. Pellagatti, M. Cazzola, A. Giagounidis, J. Perry, L. Malcovati, M. G. Della Porta, M. Jädersten, S. Killick, Amit K. Verma, C. J. Norbury, E. Hellström-Lindberg, J. S. Wainscoat, J. Boultwood

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

To gain insight into the molecular pathogenesis of the myelodysplastic syndromes (MDS), we performed global gene expression profiling and pathway analysis on the hematopoietic stem cells (HSC) of 183 MDS patients as compared with the HSC of 17 healthy controls. The most significantly deregulated pathways in MDS include interferon signaling, thrombopoietin signaling and the Wnt pathways. Among the most significantly deregulated gene pathways in early MDS are immunodeficiency, apoptosis and chemokine signaling, whereas advanced MDS is characterized by deregulation of DNA damage response and checkpoint pathways. We have identified distinct gene expression profiles and deregulated gene pathways in patients with del(5q), trisomy 8 or 7/del(7q). Patients with trisomy 8 are characterized by deregulation of pathways involved in the immune response, patients with 7/del(7q) by pathways involved in cell survival, whereas patients with del(5q) show deregulation of integrin signaling and cell cycle regulation pathways. This is the first study to determine deregulated gene pathways and ontology groups in the HSC of a large group of MDS patients. The deregulated pathways identified are likely to be critical to the MDS HSC phenotype and give new insights into the molecular pathogenesis of this disorder, thereby providing new targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)756-764
Number of pages9
JournalLeukemia
Volume24
Issue number4
DOIs
StatePublished - Apr 2010

Fingerprint

Myelodysplastic Syndromes
Hematopoietic Stem Cells
Gene Expression
Thrombopoietin
Gene Ontology
Wnt Signaling Pathway
Gene Expression Profiling
Transcriptome
Chemokines
Integrins
Interferons
Genes
DNA Damage
Cell Survival
Cell Cycle
Apoptosis
Phenotype

Keywords

  • Gene expression pathways
  • Gene expression profiling
  • Hematopoietic stem cells
  • Myelodysplastic syndromes

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Pellagatti, A., Cazzola, M., Giagounidis, A., Perry, J., Malcovati, L., Della Porta, M. G., ... Boultwood, J. (2010). Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells. Leukemia, 24(4), 756-764. https://doi.org/10.1038/leu.2010.31

Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells. / Pellagatti, A.; Cazzola, M.; Giagounidis, A.; Perry, J.; Malcovati, L.; Della Porta, M. G.; Jädersten, M.; Killick, S.; Verma, Amit K.; Norbury, C. J.; Hellström-Lindberg, E.; Wainscoat, J. S.; Boultwood, J.

In: Leukemia, Vol. 24, No. 4, 04.2010, p. 756-764.

Research output: Contribution to journalArticle

Pellagatti, A, Cazzola, M, Giagounidis, A, Perry, J, Malcovati, L, Della Porta, MG, Jädersten, M, Killick, S, Verma, AK, Norbury, CJ, Hellström-Lindberg, E, Wainscoat, JS & Boultwood, J 2010, 'Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells', Leukemia, vol. 24, no. 4, pp. 756-764. https://doi.org/10.1038/leu.2010.31
Pellagatti A, Cazzola M, Giagounidis A, Perry J, Malcovati L, Della Porta MG et al. Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells. Leukemia. 2010 Apr;24(4):756-764. https://doi.org/10.1038/leu.2010.31
Pellagatti, A. ; Cazzola, M. ; Giagounidis, A. ; Perry, J. ; Malcovati, L. ; Della Porta, M. G. ; Jädersten, M. ; Killick, S. ; Verma, Amit K. ; Norbury, C. J. ; Hellström-Lindberg, E. ; Wainscoat, J. S. ; Boultwood, J. / Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells. In: Leukemia. 2010 ; Vol. 24, No. 4. pp. 756-764.
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