Siwarski D, Müller U, Andersson J, Notario V, Melchers F, Rolink A, Huppi K
Lab of Genetics, NCI, Bethesda, MD, USA.
Curr Top Microbiol Immunol. 1997;224:67-72. doi: 10.1007/978-3-642-60801-8_6.
A chromosomal translocation (Tx) that interrupts the transcription of either c-Myc or Pvt 1 is the principal lesion in many B cell malignancies including Burkitt's Lymphoma (BL), AIDs-NHL, mouse plasmacytoma (Pct) and possibly multiple myeloma (MM). There is a restriction associated with this Tx such that only the immunoglobulin (Ig) heavy chain gene is found juxtaposed to c-Myc and only the Ig light chain gene is found juxtaposed to Pvt 1. Over the past several years, our laboratory has been instrumental in the elucidation of the structure of the mouse Pvt 1 locus as a means of understanding the relationship between these two divergent Txs which, nevertheless, produce indistinguishable disease phenotypes. In the mouse, we have identified a uniform Pvt1/Ig Ck fusion product which is consistently found in all tumors harboring Pvt 1 associated Txs. We have recently constructed transgenic mice harboring a translocated Pvt 1/Ck segment in order to determine whether 1). these mice produce the Pvt 1/Ck fusion product 2). these mice are immunocompromised and 3). these mice develop tumors of a B cell origin.
一种中断c-Myc或Pvt 1转录的染色体易位（Tx）是许多B细胞恶性肿瘤的主要病变，包括伯基特淋巴瘤（BL）、艾滋病相关非霍奇金淋巴瘤（AIDs-NHL）、小鼠浆细胞瘤（Pct）以及可能的多发性骨髓瘤（MM）。这种易位存在一种限制，即只有免疫球蛋白（Ig）重链基因与c-Myc并列，只有Ig轻链基因与Pvt 1并列。在过去几年里，我们实验室在阐明小鼠Pvt 1基因座的结构方面发挥了重要作用，以此作为理解这两种不同易位之间关系的一种手段，尽管它们产生难以区分的疾病表型。在小鼠中，我们已经鉴定出一种一致的Pvt1/Ig Ck融合产物，在所有携带与Pvt 1相关易位的肿瘤中都能持续发现。我们最近构建了携带易位的Pvt 1/Ck片段的转基因小鼠，以确定：1）这些小鼠是否产生Pvt 1/Ck融合产物；2）这些小鼠是否免疫功能低下；3）这些小鼠是否会发生B细胞起源的肿瘤。
