Home LiteratureArticle Details
PMID: 1317574 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Expression pattern of the RAR alpha-PML fusion gene in acute promyelocytic leukemia.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 11 ·1992-06-01 ·Pages 4840-4

Alcalay M, Zangrilli D, Fagioli M, Pandolfi PP, Mencarelli A, Lo Coco F, Biondi A, Grignani F, Pelicci PG

Abstract

Two chimeric genes, PML-RAR alpha and RAR alpha-PML, are formed as a consequence of the acute promyelocytic leukemia (APL)-specific reciprocal translocation of chromosomes 15 and 17 [t(15;17)]. PML-RAR alpha is expressed as a fusion protein. We investigated the organization and expression pattern of the RAR alpha-PML gene in a series of APL patients representative of the molecular heterogeneity of the t(15;17) and found (i) two types of RAR alpha-PML mRNA junctions (RAR alpha exon 2/PML exon 4 or RAR alpha exon 2/PML exon 7) that maintain the RAR alpha and PML longest open reading frames aligned and are the result of chromosome 15 breaking at two different sites; and (ii) 10 different RAR alpha-PML fusion transcripts that differ for the assembly of their PML coding exons. A RAR alpha-PML transcript was present in most, but not all, APL patients.

Related Genes
PML RARA
MeSH Terms
Base Sequence Carrier Proteins/genetics Chromosome Mapping Chromosomes, Human, Pair 15 Chromosomes, Human, Pair 17 Exons Gene Expression Genes Humans Leukemia, Promyelocytic, Acute/genetics Molecular Sequence Data Oligodeoxyribonucleotides/chemistry Polymerase Chain Reaction Protein-Tyrosine Kinases Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-bcr RNA, Messenger/genetics RNA, Neoplasm/genetics Receptors, Retinoic Acid Transcription Factors/genetics Translocation, Genetic Zinc Fingers
Chemicals
Carrier Proteins Oligodeoxyribonucleotides Proto-Oncogene Proteins RNA, Messenger RNA, Neoplasm Receptors, Retinoic Acid Transcription Factors Protein-Tyrosine Kinases BCR protein, human Proto-Oncogene Proteins c-bcr
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Alcalay M
Istituto Clinica Medica I, University of Perugia, Policlinico Monteluce, Italy.
Zangrilli D
Fagioli M
Pandolfi P P
Mencarelli A
Lo Coco F
Biondi A
Grignani F
Pelicci P G
References (15)
15 references, click to expand
  1. Molecular evaluation of response to all-trans-retinoic acid therapy in patients with acute promyelocytic leukemia.
    Blood. 1991 Apr 15;77(8):1657-9 PMID: 1849758
  2. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR.
    Cell. 1991 Aug 23;66(4):675-84 PMID: 1652369
  3. Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17.
    Science. 1990 Sep 28;249(4976):1577-80 PMID: 2218500
  4. Nuclear receptors enhance our understanding of transcription regulation.
    Trends Genet. 1988 Nov;4(11):309-14 PMID: 2853466
  5. Structure and origin of the acute promyelocytic leukemia myl/RAR alpha cDNA and characterization of its retinoid-binding and transactivation properties.
    Oncogene. 1991 Jul;6(7):1285-92 PMID: 1650447
  6. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML.
    Cell. 1991 Aug 23;66(4):663-74 PMID: 1652368
  7. Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus.
    Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1977-81 PMID: 1848017
  8. RAR-alpha gene rearrangements as a genetic marker for diagnosis and monitoring in acute promyelocytic leukemia.
    Blood. 1991 Apr 1;77(7):1418-22 PMID: 1849030
  9. Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-alpha).
    Mol Cell Biol. 1990 May;10(5):2154-63 PMID: 1970118
  10. Rearrangements and aberrant expression of the retinoic acid receptor alpha gene in acute promyelocytic leukemias.
    J Exp Med. 1990 Dec 1;172(6):1571-5 PMID: 2175343
  11. A human retinoic acid receptor which belongs to the family of nuclear receptors.
    Nature. 1987 Dec 3-9;330(6147):444-50 PMID: 2825025
  12. Identification of a receptor for the morphogen retinoic acid.
    Nature. 1987 Dec 17-23;330(6149):624-9 PMID: 2825036
  13. The steroid and thyroid hormone receptor superfamily.
    Science. 1988 May 13;240(4854):889-95 PMID: 3283939
  14. Genomic variability and alternative splicing generate multiple PML/RAR alpha transcripts that encode aberrant PML proteins and PML/RAR alpha isoforms in acute promyelocytic leukaemia.
    EMBO J. 1992 Apr;11(4):1397-407 PMID: 1314166
  15. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus.
    Nature. 1990 Oct 11;347(6293):558-61 PMID: 2170850
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.11.4840
Published
1992-06-01
Pages
4840-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC49183
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.89.11.4840 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2