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PMID: 8384553 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia.

The EMBO journal ·Vol. 12 ·No. 3 ·1993-03-00 ·Pages 1161-7

Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, Waxman S, Zelent A

Abstract

We have identified a unique case of acute promyelocytic leukaemia (APL) with a t(11;17) reciprocal chromosomal translocation involving the retinoic acid receptor alpha (RAR alpha) and a previously uncharacterized zinc finger gene. As a result of this translocation, mRNAs containing the coding sequences of the new gene, fused in-frame either upstream of the RAR alpha B region or downstream from the unique A1 and A2 regions of the two major RAR alpha isoforms, are expressed from the rearranged alleles. The above gene, which we have termed PLZF (for promyelocytic leukaemia zinc finger), encodes a potential transcription factor containing nine zinc finger motifs related to the Drosophila gap gene Krüppel and is expressed as at least two isoforms which differ in the sequences encoding the N-terminal region of the protein. Within the haematopoietic system the PLZF mRNAs were detected in the bone marrow, early myeloid cell lines and peripheral blood mononuclear cells, but not in lymphoid cell lines or tissues. In addition, the PLZF mRNA levels were down-regulated in NB-4 and HL-60 promyelocytic cell lines in response to retinoic acid-induced granulocytic differentiation and were very low in mature granulocytes. Our results demonstrate for the first time the association of a variant chromosomal translocation involving the RAR alpha gene with APL, further implicating the RAR alpha in leukaemogenesis and also suggesting an important role for PLZF as well as retinoic acid and its receptors in myeloid maturation.

Related Genes
PLZF
MeSH Terms
Amino Acid Sequence Base Sequence Carrier Proteins/genetics Cell Line Chimera Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 17 Cloning, Molecular DNA, Neoplasm Humans Leukemia, Promyelocytic, Acute/genetics Molecular Sequence Data Polymerase Chain Reaction RNA, Messenger/genetics Receptors, Retinoic Acid Translocation, Genetic Tretinoin/metabolism Zinc Fingers/genetics
Chemicals
Carrier Proteins DNA, Neoplasm RNA, Messenger Receptors, Retinoic Acid Tretinoin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Chen Z
Shanghai Institute of Haematology, Rui-Jin Hospital, Shanghai Second Medical University, China.
Brand N J
Chen A
Chen S J
Tong J H
Wang Z Y
Waxman S
Zelent A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-03-00
Pages
1161-7
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413318
Subset
IM
Databases
GENBANK
Z19002
External Links
PubMed source PMC Full Text View journal details
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