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Identification and Validation of the Anaplastic Large Cell Lymphoma Signature

  • Roberto Piva
  • Elisa Pellegrino
  • Giorgio Inghirami
Part of the Advances In Experimental Medicine And Biology book series (AEMB, volume 604)

Anaplastic large cell lymphomas (ALCL) represent a subset of lymphomas in which the anaplastic lymphoma kinase (ALK) gene is fused to several partners, most frequently to the NPM gene. We have previously demonstrated that the constitutive expression and phosphorylation of ALK chimeric proteins is sufficient for cellular transformation, and its activity is strictly required for the survival of ALCL cells. To unravel signaling pathways required for NPM–ALK-mediated transformation and tumor maintenance, we analyzed the transcriptomes of ALK positive ALCL cell lines through experimentally controlled approaches in which ALK signaling was abrogated by an inducible ALKshRNA or by ALK inhibitors. Transcripts derived from the gene expression profiling analyses uncovered a reproducible signature, which includes a novel group of ALK-regulated genes. A functional RNAi screening identified new ALK transcriptional targets instrumental to cell transformation and/or to sustain the growth and survival of ALK positive ALCL cells. Thus, we prove that an experimentally controlled and functionally validated gene expression profiling analysis represents a powerful tool to identify novel pathogenetic networks and to validate biologically suitable target genes for therapeutic interventions.

Keywords

Anaplastic Lymphoma Kinase Anaplastic Large Cell Lymphoma Gene Expression Profile Analysis Anaplastic Lymphoma Kinase Inhibitor Anaplastic Lymphoma Kinase Fusion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2007

Authors and Affiliations

  • Roberto Piva
    • 1
  • Elisa Pellegrino
    • 1
  • Giorgio Inghirami
    • 1
  1. 1.Department of Pathology and Center for Experimental Research and Medical StUniversity of TorinoItaly

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