Commonly dysregulated genes in murine APL cells

To identify genes that are commonly dysregulated in a murine model of acute promyelocytic leukemia (APL), we first defined gene expression patterns during normal murine myeloid development; serial gene expression profiling studies were performed with primary murine hematopoietic progenitors that were induced to undergo myelold maturation in vitro with G-CSF Many genes were reproducibly expressed in restricted developmental "windows," suggesting a structured hierarchy of expression that is relevant for the induction of developmental fates and/or differentiated cell functions. We compared the normal myeloid developmental transcriptome with that of APL cells derived from mice expressing PML-RAR alpha under control of the murine cathepsin G locus. While many promyelocytespecific genes were highly expressed in all APL samples, 116 genes were reproducibly dysiregulated in many independent APL samples, including Fos, Jun, Egr1, Thf, and Vcam1. However, this set of commonly dysiregulated genes was expressed normally in preleukemic, early myelold cells from the same mouse model, suggesting that dysregulation occurs as a "downstream" event during disease progression. These studies suggest that the genetic events that lead to APL progression may converge on common pathways that are important for leukemia pathogenesis.