THE PML-RAR-ALPHA FUSION MESSENGER-RNA GENERATED BY THE T(15-17) TRANSLOCATION IN ACUTE PROMYELOCYTIC LEUKEMIA ENCODES A FUNCTIONALLY ALTERED RAR

被引：1261

作者：

DETHE, H

LAVAU, C

MARCHIO, A

CHOMIENNE, C

DEGOS, L

DEJEAN, A

机构：

[1] UNIV PARIS 07,BIOL CELLULAIRE HEMATOPOET LAB,F-75221 PARIS 05,FRANCE

[2] HOP ST LOUIS,SERV CLIN MALAD SANG,F-75010 PARIS,FRANCE

[3] HOP ST LOUIS,SERV MED NUCL,F-75010 PARIS,FRANCE

[4] HOP ST LOUIS,INSERM,U93,F-75010 PARIS,FRANCE

来源：

CELL | 1991年 / 66卷 / 04期

关键词：

D O I：

10.1016/0092-8674(91)90113-D

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have previously shown that the t(15; 17) translocation specifically associated with acute promyelocytic leukemia (APL) fuses the retinoic acid receptor-alpha (RAR-alpha) locus to an as yet unknown gene, initially called myl and now renamed PML. We report here that this gene product contains a novel zinc finger motif common to several DNA-binding proteins. The PML-RAR-alpha mRNA encodes a predicted 106 kd chimeric protein containing most of the PML sequences fused to a large part of RAR-alpha, including its DNA- and hormone-binding domains. In transient expression assays, the hybrid protein exhibits altered transactivating properties if compared with the wild-type RAR-alpha progenitor. Identical PML-RAR-alpha fusion points are found in several patients. These observations suggest that in APL, the t(15;17) translocation generates an RAR mutant that could contribute to leukemogenesis through interference with promyelocytic differentiation.

引用

页码：675 / 684

页数：10

共 62 条

[1] TRANSLOCATION BREAKPOINT OF ACUTE PROMYELOCYTIC LEUKEMIA LIES WITHIN THE RETINOIC ACID RECEPTOR-ALPHA LOCUS [J].