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 ␣ (PKA-Rl␣) 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 ATRAinduced APL cell differentiation and suggests potential therapeutic alternatives for this leukemia. Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia characterized by the accumulation of cells arrested at the promyelocytic stage of myeloid differentiation. This leukemia exhibits a specific chromosomal translocation t(15;17) involving the promyelocytic leukemia (PML) gene locus on chromosome 15, and the retinoid acid receptor ␣ (RAR␣) locus on chromosome 17. This translocation generates a chimeric fusion gene PML-RAR␣, which encodes a protein that functions as an aberrant nuclear receptor considered to be the cause of APL.

It is well known that all-trans-retinoic acid (ATRA) can induce myeloid cell differentiation in acute promyelocytic leukemia (APL) cells. In this study, we found that ATRA treatment of the APL cell line NB4 induced the expression of CD52, both at transcriptional and translational levels.