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Integrated Transcript and Genome Analyses Reveal NKX2-1 and MEF2C as Potential Oncogenes in T Cell Acute Lymphoblastic Leukemia

  • Irene Homminga
  • , Rob Pieters
  • , Anton W. Langerak
  • , Johan J. de Rooi
  • , Andrew Stubbs
  • , Monique Verstegen
  • , Maartje Vuerhard
  • , Jessica Buijs-Gladdines
  • , Clarissa Kooi
  • , Petra Klous
  • , Pieter van Vlierberghe
  • , Adolfo A. Ferrando
  • , Jean Michel Cayuela
  • , Brenda Verhaaf
  • , H. Berna Beverloo
  • , Martin Horstmann
  • , Valerie de Haas
  • , Anna Sophia Wiekmeijer
  • , Karin Pike-Overzet
  • , Frank J.T. Staal
  • Wouter de Laat, Jean Soulier, Francois Sigaux, Jules P.P. Meijerink

Research output: Contribution to journalArticlepeer-review

335 Citations (Scopus)

Abstract

To identify oncogenic pathways in T cell acute lymphoblastic leukemia (T-ALL), we combined expression profiling of 117 pediatric patient samples and detailed molecular-cytogenetic analyses including the Chromosome Conformation Capture on Chip (4C) method. Two T-ALL subtypes were identified that lacked rearrangements of known oncogenes. One subtype associated with cortical arrest, expression of cell cycle genes, and ectopic NKX2-1 or NKX2-2 expression for which rearrangements were identified. The second subtype associated with immature T cell development and high expression of the MEF2C transcription factor as consequence of rearrangements of MEF2C, transcription factors that target MEF2C, or MEF2C-associated cofactors. We propose NKX2-1, NKX2-2, and MEF2C as T-ALL oncogenes that are activated by various rearrangements.

Original languageEnglish
Pages (from-to)484-497
Number of pages14
JournalCancer Cell
Volume19
Issue number4
DOIs
Publication statusPublished - 12 Apr 2011
Externally publishedYes

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