Differential regulation of gene expression following CD40 activation of leukemic compared to healthy B cells

Clair S. Gricks, David Zahrieh, A. Jason Zauls, Gullu Gorgun, Daniela Drandi, Katja Mauerer, Donna Neuberg, John G. Gribben

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

It is possible to differentiate malignant from healthy cells and to classify diseases based on identification of specific gene expression profiles. We hypothesized that gene expression profiling could also be used to identify differential activation of healthy and malignant cells, and as a model for this, we examined the molecular sequelae of CD40 activation of healthy and B-cell chronic lymphocytic leukemia (CLL) cells. Hierarchical clustering analysis of gene expression signatures grouped samples by CD40 activation status and further subclassified CD40-activated CLL cells from healthy B cells. Supervised analyses in healthy B cells compared to CLL cells identified differential regulation of genes governing cell cycle progression and apoptosis. CD40 signaling of CLL cells increases their susceptibility to immune recognition, but promotes survival and cell cycle arrest, making these cells potentially more resistant to chemotherapy. These results illustrate the utility of gene expression profiling to elucidate the molecular sequelae of signaling in healthy cells and altered signaling pathways in malignant cells. This type of approach should be useful to identify targets of therapy of malignant diseases.

Original languageEnglish (US)
Pages (from-to)4002-4009
Number of pages8
JournalBlood
Volume104
Issue number13
DOIs
StatePublished - Dec 15 2004

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Gricks, C. S., Zahrieh, D., Zauls, A. J., Gorgun, G., Drandi, D., Mauerer, K., Neuberg, D., & Gribben, J. G. (2004). Differential regulation of gene expression following CD40 activation of leukemic compared to healthy B cells. Blood, 104(13), 4002-4009. https://doi.org/10.1182/blood-2004-02-0494