Nishii K, Katayama N, Miwa H, Shikami M, Usui E, Masuya M, Araki H, Lorenzo F, Ogawa T, Kyo T, Nasu K, Shiku H, Kita K
The Second Department of Internal Medicine, Mie University School of Medicine, Japan.
Leukemia. 2002 Jul;16(7):1285-92. doi: 10.1038/sj.leu.2402533.
Ikaros, a zinc finger transcription factor, is essential for lymphoid development. Mutant mice expressing dominant-negative Ikaros gene (Ikaros) isoforms develop an aggressive form of lymphoid malignancies. We examined the expression of Ikaros isoforms in 11 leukemic cell lines and adult acute lymphoblastic leukemia cells from 36 patients with B-precursor acute lymphoblastic leukemia (pre-B ALL) and nine with T-precursor acute lymphoblastic leukemia (pre-T ALL), using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. In one pre-B ALL cell line, INC cells, and primary leukemic cells from 16 patients with pre-B ALL, we found the predominant expression of a non-DNA-binding Ikaros isoform, Ik-6. However, Ik-6 was not detected in pre-T ALL cells. All of pre-B ALL cells expressing Ik-6 were CD10(+), whereas CD10(-) pre-B ALL cells did not express Ik-6. The expression of Ik-6 was not related to karyotype abnormalities such as t(9;22) and t(4;11). Proteins from the cells that expressed Ik-6 alone failed to bind to the Ikaros protein-specific binding sequence in DNA. Ikaros proteins lacking the DNA binding sequences were detected in the cytoplasm but not in the nucleus of the cells. When INC and primary pre-B ALL cells that express Ik-6 alone were irradiated and cultured in the absence of serum, these cells produced functional Ikaros isoforms, Ik-1 and Ik-2. Purified CD19(+) CD10(-) and CD19(+) CD10(+) cells from normal human bone marrow did not express Ik-6. The predominant expression of Ik-6, which is the result of post-transcription dysregulation, is characteristic of adult pre-B ALL, especially CD10(+) pre-B ALL.
Ikaros是一种锌指转录因子，对淋巴细胞发育至关重要。表达显性负性Ikaros基因（Ikaros）异构体的突变小鼠会发生侵袭性淋巴细胞恶性肿瘤。我们使用逆转录聚合酶链反应（RT-PCR）分析，检测了11种白血病细胞系以及36例B前体急性淋巴细胞白血病（前B-ALL）患者和9例T前体急性淋巴细胞白血病（前T-ALL）患者的成人急性淋巴细胞白血病细胞中Ikaros异构体的表达。在一个前B-ALL细胞系INC细胞以及16例前B-ALL患者的原发性白血病细胞中，我们发现一种非DNA结合性Ikaros异构体Ik-6占主导性表达。然而，在前T-ALL细胞中未检测到Ik-6。所有表达Ik-6的前B-ALL细胞均为CD10(+)，而CD10(-)的前B-ALL细胞不表达Ik-6。Ik-6的表达与诸如t(9;22)和t(4;11)等核型异常无关。仅表达Ik-6的细胞中的蛋白质无法与DNA中的Ikaros蛋白特异性结合序列结合。在细胞的细胞质中检测到了缺乏DNA结合序列的Ikaros蛋白，但在细胞核中未检测到。当单独表达Ik-6的INC细胞和原发性前B-ALL细胞受到照射并在无血清条件下培养时，这些细胞产生了功能性Ikaros异构体Ik-1和Ik-2。来自正常人骨髓的纯化CD19(+) CD10(-)和CD19(+) CD10(+)细胞不表达Ik-6。Ik-6的占主导性表达是转录后失调的结果，是成人前B-ALL尤其是CD10(+)前B-ALL的特征。
