共 139 条
RARA fusion genes in acute promyelocytic leukemia: a review
被引:92
作者:

De Braekeleer, Etienne
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机构:
Univ Brest, Fac Med & Sci Sante, Lab Histol Embryol & Cytogenet, Brest, France
German Canc Res Ctr, Div Stem Cells & Canc, Heidelberg, Germany
Heidelberg Inst Stem Cell Technol & Expt Med GmbH, Heidelberg, Germany Univ Brest, Fac Med & Sci Sante, Lab Histol Embryol & Cytogenet, Brest, France

Douet-Guilbert, Nathalie
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h-index: 0
机构:
Univ Brest, Fac Med & Sci Sante, Lab Histol Embryol & Cytogenet, Brest, France
INSERM, U1078, Brest, France
CHRU Brest, Hop Morvan, Serv Cytogenet Cytol & Biol Reprod, F-29609 Brest, France Univ Brest, Fac Med & Sci Sante, Lab Histol Embryol & Cytogenet, Brest, France

De Braekeleer, Marc
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h-index: 0
机构:
Univ Brest, Fac Med & Sci Sante, Lab Histol Embryol & Cytogenet, Brest, France
INSERM, U1078, Brest, France
CHRU Brest, Hop Morvan, Serv Cytogenet Cytol & Biol Reprod, F-29609 Brest, France
CHRU Brest, Hop Morvan, Lab Cytogenet, F-29609 Brest, France Univ Brest, Fac Med & Sci Sante, Lab Histol Embryol & Cytogenet, Brest, France
机构:
[1] Univ Brest, Fac Med & Sci Sante, Lab Histol Embryol & Cytogenet, Brest, France
[2] German Canc Res Ctr, Div Stem Cells & Canc, Heidelberg, Germany
[3] Heidelberg Inst Stem Cell Technol & Expt Med GmbH, Heidelberg, Germany
[4] INSERM, U1078, Brest, France
[5] CHRU Brest, Hop Morvan, Serv Cytogenet Cytol & Biol Reprod, F-29609 Brest, France
[6] CHRU Brest, Hop Morvan, Lab Cytogenet, F-29609 Brest, France
关键词:
acute promyelocytic leukemia;
chromosomal aberrations;
fusion genes;
RARA;
treatment;
RETINOIC ACID RECEPTOR;
POLYMERASE-CHAIN-REACTION;
ACUTE MYELOID-LEUKEMIA;
LIGAND-BINDING DOMAIN;
PML/RAR-ALPHA-PROTEIN;
VARIANT TRANSLOCATION;
ARSENIC TRIOXIDE;
MESSENGER-RNA;
MOLECULAR CHARACTERIZATION;
T(15-17) TRANSLOCATION;
D O I:
10.1586/17474086.2014.903794
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
The t(15;17)(q24;q21), generating a PML-RARA fusion gene, is the hallmark of acute promyelocytic leukemia (APL). At present, eight other genes fusing with RARA have been identified. The resulting fusion proteins retain domains of the RARA protein allowing binding to retinoic acid response elements (RARE) and dimerization with the retinoid X receptor protein (RXRA). They participate in protein-protein interactions, associating with RXRA to form hetero-oligomeric complexes that can bind to RARE. They have a dominant-negative effect on wild-type RARA/RXRA transcriptional activity. Moreover, RARA fusion proteins can homodimerize, conferring the ability to regulate an expanded repertoire of genes normally not affected by RARA. RARA fusion proteins behave as potent transcriptional repressors of retinoic acid signalling, inducing a differentiation blockage at the promyelocyte stage which can be overcome with therapeutic doses of ATRA or arsenic trioxide. However, resistance to these two drugs is a major problem, which necessitates development of new therapies.
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页码:347 / 357
页数:11
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UNIV WISCONSIN,DEPT PATHOL & LAB MED,MADISON,WI UNIV WISCONSIN,DEPT PATHOL & LAB MED,MADISON,WI

CampbellDwyer, EJ
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UNIV WISCONSIN,DEPT PATHOL & LAB MED,MADISON,WI UNIV WISCONSIN,DEPT PATHOL & LAB MED,MADISON,WI

Salvato, MS
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[10]
MOLECULAR ANALYSIS OF ACUTE PROMYELOCYTIC LEUKEMIA BREAKPOINT CLUSTER REGION ON CHROMOSOME-17
[J].
BORROW, J
;
GODDARD, AD
;
SHEER, D
;
SOLOMON, E
.
SCIENCE,
1990, 249 (4976)
:1577-1580

BORROW, J
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IMPERIAL CANC RES FUND,HUMAN CYTOGENET LAB,LONDON WC2A 3PX,ENGLAND IMPERIAL CANC RES FUND,HUMAN CYTOGENET LAB,LONDON WC2A 3PX,ENGLAND

GODDARD, AD
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SHEER, D
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SOLOMON, E
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IMPERIAL CANC RES FUND,HUMAN CYTOGENET LAB,LONDON WC2A 3PX,ENGLAND IMPERIAL CANC RES FUND,HUMAN CYTOGENET LAB,LONDON WC2A 3PX,ENGLAND