Molecular profiling of CD34+ cells in idiopathic myelofibrosis identifies a set of disease-associated genes and reveals the clinical significance of Wilms' tumor gene 1 (WT1)

Paola Guglielmelli, Roberta Zini, Costanza Bogani, Simona Salati, Alessandro Pancrazzi, Elisa Bianchi, Francesco Mannelli, Sergio Ferrari, Marie Caroline Le Bousse-Kerdilès, Alberto Bosi, Giovanni Barosi, Anna Rita Migliaccio, Rossella Manfredini, Alessandro M. Vannucchi

Research output: Contribution to journalArticle

Abstract

This study was aimed at the characterization of a gene expression signature of the pluripotent hematopoietic CD34+ stem cell in idiopathic myelofibrosis (IM), which would eventually provide novel pathogenetic insights and/or diagnostic/prognostic information. Aberrantly regulated genes were revealed by transcriptome comparative microarray analysis of normal and IM CD34+ cells; selected genes were also assayed in granulocytes. One-hundred seventy four differentially expressed genes were identified and in part validated by quantitative polymerase chain reaction. Altered gene expression was corroborated by the detection of abnormally high CD9 or CD164, and low CXCR4, membrane protein expression in IM CD34+ cells. According to class prediction analysis, a set of eight genes (CD9, GAS2, DLK1, CDH1, WT1, NFE2, HMGA2, and CXCR4) properly recognized IM from normal CD34 + cells. These genes were aberrantly regulated also in IM granulocytes that could be reliably differentiated from control polycythemia vera and essential thrombocythemia granulocytes in 100% and 81% of cases, respectively. Abnormal expression of HMGA2 and CXCR4 in IM granulocytes was dependent on the presence and the mutational status of JAK2V617F mutation. The expression levels of both CD9 and DLK1 were associated with the platelet count, whereas higher WT1 expression levels identified IM patients with more active disease, as revealed by elevated CD34+ cell count and higher severity score. In conclusion, molecular profiling of IM CD34+ cells uncovered a limited number of genes with altered expression that, beyond their putative role in disease pathogenesis, are associated with patients' clinical characteristics and may have potential prognostic application.

Original languageEnglish
Pages (from-to)165-173
Number of pages9
JournalStem Cells
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 2007

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Keywords

  • CD34 cells
  • Gene expression profiling
  • Idiopathic myelofibrosis
  • JAK2 mutation
  • WT1

ASJC Scopus subject areas

  • Cell Biology

Cite this

Guglielmelli, P., Zini, R., Bogani, C., Salati, S., Pancrazzi, A., Bianchi, E., Mannelli, F., Ferrari, S., Le Bousse-Kerdilès, M. C., Bosi, A., Barosi, G., Migliaccio, A. R., Manfredini, R., & Vannucchi, A. M. (2007). Molecular profiling of CD34+ cells in idiopathic myelofibrosis identifies a set of disease-associated genes and reveals the clinical significance of Wilms' tumor gene 1 (WT1). Stem Cells, 25(1), 165-173. https://doi.org/10.1634/stemcells.2006-0351