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 myeloid 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-RARalpha under control of the murine cathepsin G locus. While many promyelocyte-specific genes were highly expressed in all APL samples, 116 genes were reproducibly dysregulated in many independent APL samples, including Fos, Jun, Egr1, Tnf, and Vcam1. However, this set of commonly dysregulated genes was expressed normally in preleukemic, early myeloid 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.
Yuan
Wenlin
W
Department of Medicine, Siteman Cancer Center, and Department of Pathology and Immunology, Washington University, St Louis, MO 63110, USA.
Payton
Jacqueline E
JE
Holt
Matthew S
MS
Link
Daniel C
DC
Watson
Mark A
MA
DiPersio
John F
JF
Ley
Timothy J
TJ
D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000235:genetics; D002454:Cell Differentiation; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D015473:Leukemia, Promyelocytic, Acute / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics
D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G; C534096:Ctsg protein, mouse