Journal
CANCER CELL
Volume 19, Issue 4, Pages 484-497Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2011.02.008
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Funding
- Dutch Cancer Society [KWF-EMCR 2006-3500]
- Children Cancer Free Foundation [KiKa 2008-029]
- German Jose Carreras Leukemia Foundation [SP 04/03]
- Children's Cancer Center Support Community Hamburg
- Ligue Contre le Cancer
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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.
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