The role of Chromosome translocation-related genes on tumorigenecity in hematological malignancie

染色体11带q23(11q23)上的染色体易位在各种白血病和淋巴瘤中被认为是一种非随机细胞遗传学事件。我们克隆了B细胞淋巴瘤的t(11；14)(q23；q32)和婴儿白血病的t(11；19)(q123；p13)断裂点，并分别在11q23、RCK和MLL上确定了目的基因。RCK基因产物是DEAD BOX蛋白/RNA解旋酶家族的成员。用Northern和Western印迹分析RCK基因的表达。Northern印迹分析表明，RCK基因的7.5kb转录本在人和小鼠组织中普遍表达。制备了针对RCK基因产物的多克隆抗体，检测了RCK基因在人和小鼠组织中的表达模式。两种不同的多克隆抗rck抗体在通过Western印迹分析测试的大多数人和小鼠组织中检测到一种名为rck/p54的特异性54kodalton产物。然而，RCK/p54在人脑中含量很低，在腰肌和肺组织中检测不到。有趣的是，来自神经母细胞瘤、胶质母细胞瘤、横纹肌肉瘤和肺癌细胞系等低表达或不表达rck/p54的恶性转化细胞产生适量的rck/p54蛋白，提示rck/p54在肿瘤发生中起作用。另一方面，15kb的转录本的MLL与果蝇的tritrax基因同源，后者是一种转录因子，参与了白血病的大量11q23易位。我们还证明了在所有病例中都发现了嵌合的MLL转录本，并且断裂点位于Zink指区的3‘侧。

The chromosome translocations ocurring at chromosome 11 band q23 (11q23) are identified as a nonrandam cytogenetic event in various kinds of leukemias and lymphomas. We cloned the breakpoints of t (11 ; 14) (q23 ; q32) in B-cell lymphoma and t (11 ; 19) (q123 ; p13) in an infantile leukemia and identified the target genes on 11q23, RCK and MLL,respectively. The RCK gene product is a member of DEAD box protein/RNA helicase family. Expression of the RCK gene was studied by Northern and Western blot analyzes. By Northern blot analysis, a 7.5 kb transcript of the RCK gene was shown to be expressed ubiquitously in human and mouse tissues. Polyclonal antibodies against RCK gene product were raised and RCK gene expression pattern was examined in human and mouse tissues. Two different polyclonal antirck antibodies detected a specific 54-kilodalton product named rck/p54 in the majority of human and mouse tissues tested by Western blot analysis. However, rck/p54 was shown to be very low in the human brain and was not detectable in lumbar muscle and lung tissues. Interestingly, malignant transformed human cells arising from the tissues with low or no expression of rck/p54, such as neuroblastoma, glioblastoma, rhabdomyosarcoma and lung cancer cell lines produced a moderate amount of rck/p54 protein, suggesting that rck/p54 plays a role on tumorigenesis.On the other hand, the MLL of 15 kb transcript was shown to be homologous to the tritrax gene of Drosophila, which is a transcription factor, and involved in vast major 11q23 translocations of leukemias. We also demonstrated that the chimeric MLL transcripts are found in all cases and the breakpoints are localized to the 3' side of the zink finger region.