2009, English, Article, Journal or magazine article edition: Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML D'Andrea, Richard James (Author); Goodall, Gregory (Author); Brown, Anna Louise (Author); ...

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Physical Description
  • text
  • journal article
Published
  • USA American Society of Hematology, 2009
Language
  • English

Edition details

Title
  • Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML
Author
  • D'Andrea, Richard James (Author)
  • Goodall, Gregory (Author)
  • Brown, Anna Louise (Author)
  • Tsykin, Anna (Author)
  • Powell, Jason (Author)
  • Thomas, Daniel (Author)
  • Barry, Emma F (Author)
  • Kok, Chung (Author)
  • McClure, Barbara J (Author)
  • To, Luenbik (Author)
  • Lewis, I.D (Author)
  • Herbert, Kirsten (Author)
  • Speed, Terence (Author)
  • Asou, Norio (Author)
  • Jacob, Bindya (Author)
  • Osato, Motomi (Author)
  • Haylock, David (Author)
  • Nilsson, Susan (Author)
  • Lopez, Angel (Author)
  • Guthridge, Mark A (Author)
Published
  • USA American Society of Hematology, 2009
Physical Description
  • text
  • journal article
Part Of
  • Blood
  • vol. 114, no. 23, pp. 4859-4870
Summary
  • Deregulated cell survival programs are a classic hallmark of cancer. We have previously identified a serine residue (Ser585) in the c 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 c 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 ofOPNexpression 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 inAML and identify OPN as a potential prognostic and therapeutic target.
Terms of Use
  • Copyright 2009 American Society of Hematology
Language
  • English
Related Resource
Identifier
  • oai:urm_publish:53119859020001831
  • oai:urm_publish:53108955370001831
  • oai:urm_publish:53110559890001831
  • 0000060364-RMID
  • 2-s2.0-74049157071-EID
  • 000272190700015-WoS

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