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JMD 2003, Vol. 5, No. 4
Copyright © 2003 American Society for Investigative Pathology & Association for Molecular Pathology

Gene Expression Profiling during All-trans Retinoic Acid-Induced Cell Differentiation of Acute Promyelocytic Leukemia Cells

Lijun Yang*, Hongshan Zhao{dagger}, Shi-Wu Li*, Kim Ahrens*, Christine Collins{dagger}, Sarah Eckenrode{dagger}, Qing-guo Ruan{dagger}, Richard A. McIndoe{dagger} and Jin-Xiong She{dagger}

From the Department of Pathology, Immunology, and Laboratory Medicine, * University of Florida College of Medicine, Gainesville, Florida; and the Center for Biotechnology and Genomic Medicine, {dagger} Medical College of Georgia, Augusta, Georgia

Using cDNA microarrays we determined the gene expression patterns in the human acute promyelocytic leukemia (APL) cell line NB4 during all-trans retinoic acid (ATRA)-induced differentiation. We analyzed the expression of 12,288 genes in the NB4 cells after 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours of ATRA exposure. During this time course, we found 168 up-regulated and more than 179 down-regulated genes, most of which have not been reported before. Many of the altered genes encode products that participate in signaling pathways, cell differentiation, programmed cell death, transcription regulation, and production of cytokines and chemokines. Of interest, the CD52 and protein kinase A regulatory subunit {alpha} (PKA-Rl{alpha}) genes, whose products are being used as therapeutic targets for certain human neoplasias in currently ongoing clinical trials, were among the genes observed to be markedly up-regulated after ATRA treatment. The present study provides valuable data to further understand the mechanism of ATRA-induced APL cell differentiation and suggests potential therapeutic alternatives for this leukemia.




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