Nakase K, Ishimaru F, Avitahl N, Dansako H, Matsuo K, Fujii K, Sezaki N, Nakayama H, Yano T, Fukuda S, Imajoh K, Takeuchi M, Miyata A, Hara M, Yasukawa M, Takahashi I, Taguchi H, Matsue K, Nakao S, Niho Y, Takenaka K, Shinagawa K, Ikeda K, Niiya K, Harada M
Department of Medicine, University of Okayama, Japan.
Cancer Res. 2000 Aug 1;60(15):4062-5.
Gene targeting studies in mice have shown that the transcription factor Ikaros plays an essential role in lymphoid development and as a tumor suppressor in T cells, whereas the related gene Aiolos functions as a tumor suppressor in B cells. We analyzed the expression levels of the Ikaros gene family, Ikaros and Aiolos, in human bone marrow samples from patients with adult acute lymphoblastic leukemia [ALL (n = 46; B-cell ALL = 41; T-cell ALL = 5)]. Overexpression of the dominant negative isoform of Ikaros gene Ik-6 was observed in 14 of 41 B-cell ALL patients by reverse transcription-PCR, and the results were confirmed by sequencing analysis and immunoblotting. None of the other dominant negative isoforms of the Ikaros gene were detected by reverse transcription-PCR analysis. Southern blotting analysis with PstI digestion revealed that those patients with the dominant negative isoform Ik-6 might have small mutations in the Ikaros locus. We did not detect any overexpression of dominant negative isoforms of Aiolos in adult ALL patients. These results suggest that Ikaros plays a key role in human B-cell malignancies through the dominant negative isoform Ik-6.
对小鼠的基因靶向研究表明，转录因子IKAROS在淋巴细胞发育中起关键作用，并且在T细胞中作为肿瘤抑制因子发挥作用，而相关基因AIOLOS则在B细胞中作为肿瘤抑制因子发挥作用。我们分析了成年急性淋巴细胞白血病患者（成人急性淋巴细胞白血病[ALL（n = 46；B细胞ALL = 41；T细胞ALL = 5）]）的人骨髓样本中IKAROS基因家族、IKAROS和AIOLOS的表达水平。通过逆转录PCR在41例B细胞ALL患者中的14例中观察到IKAROS基因Ik-6的显性负性异构体的过表达，结果通过测序分析和免疫印迹得到证实。通过逆转录PCR分析未检测到IKAROS基因的其他显性负性异构体。用PstI消化进行的Southern印迹分析表明，那些具有显性负性异构体Ik-6的患者可能在IKAROS基因座中有小的突变。我们在成年ALL患者中未检测到AIOLOS显性负性异构体的任何过表达。这些结果表明，IKAROS通过显性负性异构体Ik-6在人类B细胞恶性肿瘤中起关键作用。
