Differential regulation of gene expression following CD40 activation of leukemic compared to healthy B cells.
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.
Gricks
Clair S
CS
Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 44 Binney St, Rm D520, Boston, MA 02115, USA.
Zahrieh
David
D
Zauls
A Jason
AJ
Gorgun
Gullu
G
Drandi
Daniela
D
Mauerer
Katja
K
Neuberg
Donna
D
Gribben
John G
JG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D018095:Germ-Line Mutation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D012016:Reference Values
D015703:Antigens, CD; D019013:CD40 Antigens