Comparative analysis of genes regulated by PML/RARα and PLZF/RARα in response to retinoic acid using oligonucleotide arrays

Molecular signature of retinoic acid treatment in acute promyelocytic leukemia

“…Different studies of gene expression profiling that use cell lines, either NB4 or U937, as models to study RAinduced differentiation in APL have already been published (Tamayo et al, 1999;Liu et al, 2000;Lee et al, 2002;Park et al, 2003). In order to compare our results with those of the previously published reports, we first re-annotated the published results according to UniGene release Hs.166, starting from the GeneChip probe set ID (where available), or, alternatively, from the GeneBank accession number.…”

“…Previous studies describe gene expression modifications induced by RA in cell lines (Tamayo et al, 1999;Liu et al, 2000;Lee et al, 2002;Park et al, 2003). We here present a detailed analysis of transcriptional regulation in blasts derived from APL patients prior to and after RA treatment.…”

Pro-proliferative function of the long isoform of PML-RARα involved in acute promyelocytic leukemia

“…PML-RARa is a potent and specific activator of c-fos promoter By gene array, PML-RARa upregulates 1569 and downregulates another 1726 genes (Alcalay et al, 2003;Park et al, 2003;Nouzova et al, 2004;Meani et al, 2005). Examples of repressed genes are RARb2 and C/EBPb (Di Croce et al, 2002;Duprez et al, 2003), while examples of induced genes are Cyclin A1, p21 and c-fos (Casini and Pelicci, 1999;Mu¨ller et al, 2000;Alcalay et al, 2003;Meani et al, 2005).…”

“…PML-RARa induces DNA hypermethylation and heterochromatin formation through aberrant recruitment of different chromatin modifying enzymes to specific promoters, leading to its transcriptional silencing. But PML-RARa also has been shown to upregulate a number of genes on different microarray setups (Alcalay et al, 2003;Park et al, 2003;Nouzova et al, 2004;Meani et al, 2005). Either PMLRARa has acquired new DNA-binding properties different from those of the RARa (Hauksdottir and Privalsky, 2001) such that it does not only bind to RAREs, or it can also upregulate target genes through indirect mechanisms (Duprez et al, 2003;Duprez, 2004).…”

Genomic tools for dissecting oncogenic transcriptional networks in human leukemia

“…These experiments typically require a tight control of transcription factor function, which can be readily obtained by ligand stimulation or withdrawal in the case of ligand-activated transcription factors, such as the glucocorticoid and vitamin D receptors, 11,12 and the PML-RARA acute promyelocytic leukemia fusion oncoprotein. 13 This approach has been extended to the analysis of additional transcription factors by generating fusions turning them into estrogen-activated proteins by fusion with the hormone-binding domain of the estrogen receptor. [14][15][16][17] Alternatively, a loss-offunction variation of this approach can be achieved by inactivation of the transcription factor of interest by expression of a dominant negative form of the protein or by RNA interference knockdown.…”