TY - JOUR
T1 - Genomewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells
AU - Tissing, Wim J.E.
AU - Den Boer, Monique L.
AU - Meijerink, Jules P.P.
AU - Menezes, Renee X.
AU - Swagemakers, Sigrid
AU - Van Der Spek, Peter J.
AU - Sallan, Stephen E.
AU - Armstrong, Scott A.
AU - Pieters, Rob
PY - 2007/5/1
Y1 - 2007/5/1
N2 - Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours of prednisolone exposure in leukemic cells of 13 children as compared with nonexposed cells. Following 3 hours of exposure no significant changes in gene expression could be identified. Following 8 hours of exposure, 51 genes were differentially expressed (P < .001 and false discovery rate < 10%) with 39 genes being up-regulated (median, 2.4-fold) and 12 genes were downregulated (median, 1.7-fold). Twenty-one of those genes have not been identified before to be transcriptionally regulated by prednisolone. Two of the 3 most highly up-regulated genes were tumor suppressor genes, that is, thioredoxin-interacting protein (TXNIP; 3.7-fold) and zinc finger and BTB domain containing 16 (ZBTB16; 8.8-fold). About 50% of the differentially expressed genes were functionally categorized in 3 major routes, namely MAPK pathways (9 genes), NF-κB signaling (11 genes), and carbohydrate metabolism (5 genes). Biologic characterization of these genes and pathways might elucidate the action of glucocorticoids in ALL cells, possibly suggesting causes of glucocorticoid resistance and new potential targets for therapy.
AB - Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours of prednisolone exposure in leukemic cells of 13 children as compared with nonexposed cells. Following 3 hours of exposure no significant changes in gene expression could be identified. Following 8 hours of exposure, 51 genes were differentially expressed (P < .001 and false discovery rate < 10%) with 39 genes being up-regulated (median, 2.4-fold) and 12 genes were downregulated (median, 1.7-fold). Twenty-one of those genes have not been identified before to be transcriptionally regulated by prednisolone. Two of the 3 most highly up-regulated genes were tumor suppressor genes, that is, thioredoxin-interacting protein (TXNIP; 3.7-fold) and zinc finger and BTB domain containing 16 (ZBTB16; 8.8-fold). About 50% of the differentially expressed genes were functionally categorized in 3 major routes, namely MAPK pathways (9 genes), NF-κB signaling (11 genes), and carbohydrate metabolism (5 genes). Biologic characterization of these genes and pathways might elucidate the action of glucocorticoids in ALL cells, possibly suggesting causes of glucocorticoid resistance and new potential targets for therapy.
UR - http://www.scopus.com/inward/record.url?scp=34247490700&partnerID=8YFLogxK
U2 - 10.1182/blood-2006-11-056366
DO - 10.1182/blood-2006-11-056366
M3 - Article
C2 - 17218380
AN - SCOPUS:34247490700
SN - 0006-4971
VL - 109
SP - 3929
EP - 3935
JO - Blood
JF - Blood
IS - 9
ER -