Kamps M P, Murre C, Sun X H, Baltimore D
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142.
Cell. 1990 Feb 23;60(4):547-55. doi: 10.1016/0092-8674(90)90658-2.
It was previously shown that the chromosome 19 breakpoint of the t(1;19)(q23;p13.3) translocation, found in human pre-B cell acute lymphoblastic leukemias, is within the E2A transcription factor gene on chromosome 19. A cell line with this translocation contains two novel chimeric mRNAs, both with the same 5'E2A sequences but with different lengths of 3' sequence from a previously unrecognized gene dubbed prl, located on chromosome 1. The chimeric RNAs encode a protein that lacks 171 amino acids of E2A, including its DNA binding and dimerization motifs, but have instead a homeobox-related sequence from prl. Therefore, the production of a chimeric E2A-Prl protein may contribute to the acute lymphoblastic phenotype by directly altering the expression of genes normally responsive to the Prl homeoprotein.
先前研究表明，在人类前B细胞急性淋巴细胞白血病中发现的t(1;19)(q23;p13.3)易位的19号染色体断点位于19号染色体上的E2A转录因子基因内。具有这种易位的细胞系包含两种新的嵌合mRNA，二者5'E2A序列相同，但3'序列长度不同，3'序列来自位于1号染色体上一个此前未被识别的名为prl的基因。嵌合RNA编码一种蛋白质，该蛋白质缺少E2A的171个氨基酸，包括其DNA结合和二聚化基序，但取而代之的是来自prl的与同源盒相关的序列。因此，嵌合E2A-Prl蛋白的产生可能通过直接改变通常对Prl同源蛋白有反应的基因的表达，导致急性淋巴细胞表型。
