Gishizky M L, McLaughlin J, Pendergast A M, Witte O N
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1570.
Oncogene. 1991 Aug;6(8):1299-306.
The Philadelphia chromosome (Ph1, t9:22;34:q11) is a reciprocal translocation between chromosome 22 and chromosome 9 which results in the formation of the chimeric BCR/ABL oncogene. Alternative forms of BCR/ABL are produced by splicing different sets of exons of the BCR gene to a common set of c-ABL sequences. This results in the formation of an 8.7 kilobase mRNA that encodes the P210 BCR/ABL gene product or a 7.0 kilobase mRNA that encodes the P185 BCR/ABL gene product. Both BCR/ABL transcripts derive their 5' non-coding sequences from the BCR gene locus. This 5' region is over 500 nucleotides in length, has a GC content greater than 75% and has a short open reading frame. To determine if this unusual 5' non-coding region plays a role in BCR/ABL transformation, we prepared retroviral vectors containing identical BCR/ABL coding regions but differing in the length of the BCR 5' non-coding region. Matched viral stocks were evaluated for their ability to transform bone marrow in vitro and for their ability to cause tumors when inoculated into 3- to 4-week-old mice. In this report we present the unexpected finding that the BCR/ABL 5' non-coding region augments the transforming activity of both P210 and P185 BCR/ABL in vitro. In vivo, BCR/ABL is a weak tumorigenic agent and its potency is enhanced by the presence of the 5' non-coding region.
费城染色体（Ph1，t9:22;34:q11）是22号染色体与9号染色体之间的相互易位，导致嵌合性BCR/ABL癌基因的形成。BCR/ABL的替代形式是通过将BCR基因的不同外显子组剪接到一组共同的c-ABL序列上产生的。这导致形成一个编码P210 BCR/ABL基因产物的8.7千碱基mRNA或一个编码P185 BCR/ABL基因产物的7.0千碱基mRNA。两种BCR/ABL转录本的5'非编码序列均来自BCR基因座。这个5'区域长度超过500个核苷酸，GC含量大于75%，并且有一个短的开放阅读框。为了确定这个不寻常的5'非编码区域是否在BCR/ABL转化中起作用，我们制备了逆转录病毒载体，其包含相同的BCR/ABL编码区域，但BCR 5'非编码区域的长度不同。对匹配的病毒株进行了体外转化骨髓能力以及接种到3至4周龄小鼠体内致瘤能力的评估。在本报告中，我们展示了一个意外发现，即BCR/ABL 5'非编码区域在体外增强了P210和P185 BCR/ABL的转化活性。在体内，BCR/ABL是一种弱致瘤剂，其效力因5'非编码区域的存在而增强。
