TRANSLOCATION BREAKPOINT OF ACUTE PROMYELOCYTIC LEUKEMIA LIES WITHIN THE RETINOIC ACID RECEPTOR-ALPHA LOCUS
TRANSLOCATION BREAKPOINT OF ACUTE PROMYELOCYTIC LEUKEMIA LIES WITHIN THE RETINOIC ACID RECEPTOR-ALPHA LOCUS
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DOI：
10.1073/pnas.88.5.1977
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发表时间：
1991-03-01
影响因子：
11.1
通讯作者：
PELICCI, PG
中科院分区：
文献类型：
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作者：
ALCALAY, M;ZANGRILLI, D;PELICCI, PG
急性早幼粒细胞白血病 (APL) 的特点是涉及 15 号和 17 号染色体的相互平衡易位 [t(15;17)]。 我们报告了两个相互断裂位点之一的分离和表征，并证明 17 号染色体断裂点位于视黄酸受体-α 基因座内。 15q+ 上 15;17 交叉连接点的核苷酸测序表明，视黄酸受体-α 基因在其第一个内含子内（外显子 II 剪接供体位点上游 370 个碱基对）内被截短。 这种重组预计会产生异常的 RAR-α mRNA 和蛋白质。 使用 15 号染色体和 17 号染色体衍生的 DNA 探针对许多 APL 进行 Southern 印迹分析，发现大多数其他 APL 中存在类似的 15;17 重组。 我们的数据强有力地证明视黄酸受体-α 基因在 APL 的白血病发生中起着至关重要的作用。
Acute promyelocytic leukemias (APLs) are characterized by a reciprocal balanced translocation that involves chromosomes 15 and 17 [t(15;17)]. We report the isolation and characterization of one of the two reciprocal break sites and demonstrate that the chromosome 17 breakpoint lies within the retinoic acid receptor-alpha locus. Nucleotide sequencing of the 15;17 cross-over junction on 15q+ showed that the retinoic acid receptor-alpha gene is truncated within its first intron, 370 base pairs upstream from the splicing donor site of exon II. Such a recombination would be expected to generate abnormal RAR-alpha mRNA and protein. Southern blot analysis of a number of APLs with chromosome 15- and 17-derived DNA probes revealed similar 15;17 recombinations in the majority of other APLs. Our data are strong evidence that the retinoic acid receptor-alpha gene plays a crucial role in the leukemogenesis of APL.