Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
Cancer Cell. 2011 Apr 12;19(4):484-97. doi: 10.1016/j.ccr.2011.02.008.
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.
为了鉴定 T 细胞急性淋巴细胞白血病（T-ALL）中的致癌通路，我们将 117 例儿科患者样本的表达谱与详细的分子细胞遗传学分析相结合，包括染色体构象捕获芯片（4C）方法。鉴定出两种缺乏已知致癌基因重排的 T-ALL 亚型。一种亚型与皮质阻滞、细胞周期基因的表达以及 NKX2-1 或 NKX2-2 的异位表达相关，这些基因的重排已被确定。第二种亚型与不成熟 T 细胞发育相关，并且 MEF2C 转录因子的表达水平较高，这是由于 MEF2C、靶向 MEF2C 的转录因子或 MEF2C 相关辅助因子的重排所致。我们提出 NKX2-1、NKX2-2 和 MEF2C 作为 T-ALL 致癌基因，它们可被各种重排激活。
