Sakai Ikuya, Tamura Tatsushiro, Narumi Hirosi, Uchida Naoyuki, Yakushijin Yoshihiro, Hato Takaaki, Fujita Shigeru, Yasukawa Masaki
First Department of Internal Medicine, Ehime University School of Medicine, Toon, Ehime 791-0295, Japan.
Genes Chromosomes Cancer. 2005 Nov;44(3):265-70. doi: 10.1002/gcc.20241.
The t(1;21)(p36;q22) is a recurrent chromosome abnormality associated with therapy-related acute myeloid leukemia (AML). Although involvement of RUNX1 has been detected by fluorescence in situ hybridization analysis, the partner gene has not been reported previously. We identified a novel RUNX1 partner gene, MDS1/EVI1-like-gene 1 (PRDM16), in an AML patient with t(1;21). Alternative splicing of the fusion gene generates five different fusion transcripts. In two of them, the PRDM16 reading frame is maintained in the fusion with RUNX1, suggesting that the RUNX1-PRDM16 gene fusion results in the production of a protein that is highly homologous to the RUNX1-MDS1/EVI1 chimeric protein. It is suggested that PRDM16 and MDS1/EVI1 share a common molecular mechanism for the leukemogenesis of RUNX1-associated leukemia. Characterization of the RUNX1-PRDM16 fusion protein and comparison with the RUNX1-MDS1/EVI1 protein will facilitate the understanding of the mechanisms underlying RUNX1-associated leukemia.
t(1;21)(p36;q22)是一种与治疗相关的急性髓系白血病（AML）相关的复发性染色体异常。尽管通过荧光原位杂交分析检测到RUNX1受累，但此前尚未报道其伙伴基因。我们在一名患有t(1;21)的AML患者中鉴定出一个新的RUNX1伙伴基因，即MDS1/EVI1样基因1（PRDM16）。融合基因的可变剪接产生了五种不同的融合转录本。其中两种转录本中，PRDM16阅读框在与RUNX1融合时得以保留，这表明RUNX1-PRDM16基因融合导致产生一种与RUNX1-MDS1/EVI1嵌合蛋白高度同源的蛋白质。提示PRDM16和MDS1/EVI1在RUNX1相关白血病的白血病发生中具有共同的分子机制。对RUNX1-PRDM16融合蛋白的表征以及与RUNX1-MDS1/EVI1蛋白的比较将有助于理解RUNX1相关白血病的潜在机制。
