Please use this identifier to cite or link to this item:
|Title:||Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML||Authors:||Powell, J.A.
|Issue Date:||26-Nov-2009||Citation:||Powell, J.A., Thomas, D., Barry, E.F., Kok, C.H., McClure, B.J., Tsykin, A., To, L.B., Brown, A., Lewis, I.D., Herbert, K., Goodall, G.J., Speed, T.P., Asou, N., Jacob, B., Osato, M., Haylock, D.N., Nilsson, S.K., D'Andrea, R.J., Lopez, A.F., Guthridge, M.A. (2009-11-26). Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML. Blood 114 (23) : 4859-4870. ScholarBank@NUS Repository. https://doi.org/10.1182/blood-2009-02-204818||Abstract:||Deregulated cell survival programs are a classic hallmark of cancer. We have previously identified a serine residue (Ser585) in the βc subunit of the granulocyte-macrophage colony-stimulating factor receptor that selectively and independently promotes cell survival. We now show that Ser585 phosphorylation is constitutive in 20 (87%) of 23 acute myeloid leukemia (AML) patient samples, indicating that this survivalonly pathway is frequently deregulated in leukemia. We performed a global expression screen to identify gene targets of this survival pathway and report a 138-gene βc Ser585-regulated transcriptome. Pathway analysis defines a gene network enriched for PI3-kinase target genes and a cluster of genes involved in cancer and cell survival. We show that one such gene, osteopontin (OPN), is a functionally relevant target of the Ser585-survival pathway as shown by siRNA-mediated knockdown ofOPN expression that induces cell death in both AML blasts and CD34+CD38+CD123+ leukemic progenitors. Increased expression of OPN at diagnosis is associated with poor prognosis with multivariate analysis indicating that it is an independent predictor of overall patient survival in normal karyotype AML (n = 60; HR = 2.2; P = .01). These results delineate a novel cytokine-regulated Ser585/ PI3-kinase signaling network that is deregulated in AML and identify OPN as a potential prognostic and therapeutic target. © 2009 by The American Society of Hematology.||Source Title:||Blood||URI:||http://scholarbank.nus.edu.sg/handle/10635/110738||ISSN:||00064971||DOI:||10.1182/blood-2009-02-204818|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jun 15, 2021
WEB OF SCIENCETM
checked on Jun 15, 2021
checked on Jun 7, 2021
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.