BAL is a novel risk-related gene in diffuse large B-cell lymphomas that enhances cellular migration
BAL is a novel risk-related gene in diffuse large B-cell lymphomas that enhances cellular migration
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DOI：
10.1182/blood.v96.13.4328.h8004328_4328_4334
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发表时间：
2000-12-15
期刊：
影响因子：
20.3
通讯作者：
Shipp, MA
中科院分区：
文献类型：
--
作者：
Aguiar, RCT;Yakushijin, Y;Shipp, MA
临床风险因素模型，如国际预后指数，用于确定弥漫性大B细胞淋巴瘤（DLB-CL）患者的疾病死亡风险不同。为了阐明这些观察到的临床结果差异的分子基础，差异显示被用来确定一个新的基因，称为BAL（B-侵袭性淋巴瘤），这是在致命的高风险DLB-CL比治愈的低风险肿瘤表达水平显着更高。主要BAL互补DNA编码先前未表征的88-kd核蛋白，其具有与组蛋白-macroH 2A的非组蛋白部分同源的重复N-末端结构域和具有2个短卷曲螺旋结构域的C-末端α-螺旋区。值得注意的是，BAL的N-末端和二级结构类似于最近鉴定的人蛋白KIAA 1268。此外，BAL和KIAA 1268都定位于染色体3q 21，进一步表明这些基因属于一个新发现的家族。BAL在具有活化的外周B细胞而不是生发中心细胞表型的DLB-CL细胞系中以增加的水平表达。这一观察结果和高风险DLB-CL的特征性传播促使人们研究BAL在B细胞迁移中的作用。在经典的transwell检测中，稳定的BAL过表达B细胞淋巴瘤转染子的迁移率显著高于仅载体转染子，表明风险相关的BAL基因促进恶性B细胞迁移。（血。2000;96：4328-4334）（C）2000由美国血液学学会。
Clinical risk factor models such as the International prognostic Index are used to identify diffuse large B-cell lymphoma (DLB-CL) patients with different risks of death from their diseases. To elucidate the molecular bases for these observed clinical differences in outcome, differential display was used to identify a novel gene, termed BAL (B-aggressive lymphoma), which is expressed at significantly higher levels in fatal high-risk DLB-CLs than in cured low risk tumors. The major BAL complementary DNA encodes a previously uncharacterized 88-kd nuclear protein with a duplicated N-terminal domain homologous to the non- histone portion of histone-macroH2A and a C-terminal alpha-helical region with 2 short coiled-coil domains. Of note, the BAL N-terminus and secondary structure resemble those of a recently identified human protein, KIAA1268. In addition, both BAL and KIAA1268 map to chromosome 3q21, further suggesting that these genes belong to a newly identified family. BAL is expressed at increased levels in DLB-CL cell lines with an activated peripheral B cell, rather than a germinal center cell, phenotype. This observation and the characteristic dissemination of high risk DLB-CLs prompted studies regarding the role of BAL in B-cell migration. In classical transwell assays, stable BAL-overexpressing B-cell lymphoma transfectants had significantly higher rates of migration than vector-only transfectants, indicating that the risk-related BAL gene promotes malignant B-cell migration. (Blood. 2000;96:4328-4334) (C) 2000 by The American Society of Hematology.