Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia

Cancer Cell. 2011 Apr 12;19(4):484-97. doi: 10.1016/j.ccr.2011.02.008.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Female
  • Gene Expression Regulation, Leukemic
  • Gene Rearrangement
  • Genome, Human*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / physiology
  • Humans
  • Infant
  • MADS Domain Proteins / genetics*
  • MADS Domain Proteins / physiology
  • MEF2 Transcription Factors
  • Male
  • Myogenic Regulatory Factors / genetics*
  • Myogenic Regulatory Factors / physiology
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / physiology
  • Oncogenes*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / etiology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Thyroid Nuclear Factor 1
  • Transcription Factors / genetics*
  • Transcription Factors / physiology
  • Transcription, Genetic*
  • Zebrafish Proteins

Substances

  • Homeodomain Proteins
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • Myogenic Regulatory Factors
  • Nkx2.2 protein
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • Zebrafish Proteins

Associated data

  • GEO/GSE26713